Methods of using bicyclic compounds as triggering receptor expressed on myeloid cells (TREM2) agonists

Abstract

The present disclosure provides methods of using a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof to treat Alzheimer's Disease in a human subject.

Description

[0001] METHODS OF USING BICYCLIC COMPOUNDS AS TRIGGERING RECEPTOR EXPRESSED ON MYELOID CELLS (TREM2) AGONISTS CROSS REFERENCE TO RELATED APPLICATION This application claims the benefit of United States Provisional Application No. 63 / 674,790, filed July 23, 2024, United States Provisional Application No.63 / 748,276, filed January 22, 2025, and United States Provisional Application No.63 / 781,923, filed April 1, 2025, the entirety of each of which is incorporated herein by reference. TECHNICAL FIELD The present disclosure provides methods of using a TREM2 agonist for treating Alzheimer’s disease in a human patient. BACKGROUND Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is clinically characterized by cognitive impairment, behavioral disturbances, psychiatric symptoms, and disability in activities of daily living. AD is the most common cause of dementia, accounting for 60% to 80% of dementia cases. An estimated 6.7 million persons aged 65 years and older in the United States suffer from AD. It is the seventh leading cause of death among individuals aged 65 years and older and is the leading cause of disability and poor health in older adults. Pathologically, AD is characterized by extracellular beta-amyloid (Aβ) plaques and intraneuronal accumulation of neurofibrillary tangles consisting of phospho-tau. Additionally, chronic neuroinflammation, gliosis, synapse loss and neurodegeneration are hallmarks of AD. While the full complement of causal drivers of AD pathogenesis continues to be an active area of research, numerous recent human genome-wide association studies (GWAS) have converged on the dysfunction of the innate immune system as a causal driver of AD, as risk genes have been found to disproportionately affect the function of microglia compared to other central nervous system (CNS) cell types. Specifically, dysfunction in triggering receptor expressed on myeloid cells 2 (TREM2) function has been reported to exacerbate AD-associated tau accumulation and spreading (Leyns, 2019). Loss-of-function TREM2 variants occur in 7% to 8% of the AD population and are linked both to disease progression and to worsened patient outcomes. Within the CNS, TREM2 is predominantly expressed by microglia. Recent findings indicate that microglia, via normal TREM2-dependent function, influence the structure of amyloid plaques and form a barrier against plaque, conferring protection to neurons from toxic Aβ species (Wang, 2020). Alzheimer’s disease-associated TREM2 mutations within the ligand binding domain are reported to confer a partial loss of TREM2 function, and are linked to faster disease progression (Jin, 2014; Korvatska, 2015; Cheng-Hathaway, 2018; Parhizkar, 2019). The insights from large scale GWAS and related functional characterization are driving current drug discovery efforts on specific AD-implicated molecular targets and pathways, thereby cultivating the next-generation of genetic-inspired AD TREM2 agonist therapeutics. A need continues to exist in the art for a method of treating Alzheimer’s disease in a human subject. SUMMARY OF THE DISCLOSURE An aspect of the disclosure is directed to methods of treating Alzheimer’s Disease in a subject in need thereof, the method comprising administering to the subject a dosage of about 0.5 mg to about 400 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. In some embodiments of the methods described herein, the small molecule TREM2 agonist is a compound of Formula (I) having the following structure: or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein Ring A together with the 6-membered ring system to which it is fused forms a bicyclic ring system selected from:

[0002] wherein X1is CR10or N; X2is C(R10)2, O, C(=O), S(O)2, or NR10; X3is CR10or N; X4is CR10or N; X5is CR10or N; X6is CR10, N, or NR10; X7is CR10or N; X8is CR10or N; X9is CR10or N; X10is CR10, C(R10)2, O, S or NR10; X11is C or N; X12is CR10or NR10; X13is C or N; X23is CR10, N, NR10, SO2, or C=O; X24is CR10, N, NR10, SO2, or C=O; X25is CR10, N, NR10, SO2, or C=O; L is a bond or an optionally substituted straight chain or branched C1-6 alkylene; wherein the straight chain or branched C1-6 alkylene is optionally substituted with C1-6 alkyl, hydroxyl, or -N(RB)(RC); R1aand R1bis each independently H, C1-6alkyl, or C1-6heteroalkyl; R2aand R2bis each independently H, D, C1-6 alkyl, C1-6 haloalkyl, C1-6 heteroalkyl, C3- 8cycloalkyl, or C3-8 heterocyclic; R3is H, D, C1-6 alkyl, or C1-6 heteroalkyl; or R1a, R1b, and R3are taken together with their intervening atoms to form a cyclic group selected from a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring; R4is C1-6 alkyl, C2-6 alkenyl, C1-6 haloalkyl, C1-6 heteroalkyl, C3-8 cycloalkyl, C3-8 heterocycloalkyl, aryl, heteroaryl, -O(RA), -N(RB)(RC), C(=O)(C1-6alkyl), -C(=O)O(C1-6alkyl), - C(=O)(cycloalkyl), -C(=O)(heterocyclic), or -C(=O)(heteroaryl), wherein alkyl, alkenyl, haloalkyl, heteroalkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl are optionally further substituted with 1-6 R11; R5is C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C1-6 heteroalkyl, C3-8 cycloalkyl, C3-8 heterocyclic, aryl, heteroaryl, halogen, cyano, -O(RA), -N(RB)(RC), C(=O)(C1-6alkyl), - C(=O)O(C1-6alkyl), -C(=O)(cycloalkyl), -C(=O)(heterocyclic), or -C(=O)(heteroaryl), wherein alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl are optionally further substituted with 1-6 R11; R6and R7are each independently H, D, C1-6 alkyl, C2-6 alkenyl, C1-6 heteroalkyl, C1-6 haloalkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, halogen, cyano, -O(RA), or -N(RB)(RC), wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclic, aryl, and heteroaryl is optionally substituted with one or more R12; or wherein the R6and R7groups together with the carbons to which they are attached form a 5- membered heterocyclic group; R8aand R8bare each independently H or C1-6alkyl; or R8aand R8bare taken together with their intervening atoms to an oxo group; R9is H or C1-6 alkyl; R10is H, C1-6 alkyl, C1-6 heteroalkyl, C1-6 haloalkyl, heteroaryl, halogen, cyano, - O(RA), -N(RB)(RC), or -N(RB), wherein heteroaryl is optionally further substituted with 1-6 R11, or wherein any two R10groups together with the carbons to which they are attached at X23, X24, or X25form a 5-membered heterocyclic group; R11and R12are each independently H, D, C1-6 alkyl, C1-6 heteroalkyl, C1-6 haloalkyl, halogen, oxo, -O(RA), or -N(RB)(RC); each RAis independently H, D, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, cycloalkyl, heterocyclic, or -N(RB)(RC); each RBand RCis independently H, C1-6 alkyl, C1-6 heteroalkyl, C1-6 heteroaralkyl, C1-6 haloalkyl, cycloalkyl, heterocyclic, or -C(O)-alkyl, wherein the C1-6 alkyl or heterocyclic is optionally further substituted with cycloalkyl or –O(RA); R13is an optionally substituted C1-6 aliphatic group, halogen, -OR, -CN, -NR2, -C(=O)R, -C(=O)OR, -C(=O)NR2, -SO2R, -SO2NR2, C1-6haloalkyl, or C1-6haloalkoxy; n is 0, 1, or 2; and m is 0, 1, or 2. In some embodiments, the compound of Formula (I), or tautomer thereof, or pharmaceutically acceptable salt of said compound or said tautomer, is as follows: Ring A together with the 6-membered ring system to which it is fused forms a bicyclic ring system selected from:

[0003] Ring B is selected from: wherein X1is CR10or N; X2is C(R10)2, O, C(=O), S(O)2, or NR10; X3is CR10or N; X4is CR10or N; X5is CR10or N; X6is CR10or NR10; X7is CR10or N; X8is CR10or N; X9is CR10or N; X10is C(R10)2, O, S or NR10; X11is C or N; X12is CR10or NR10; X13is C or N; X23is C(R10)2, NR10, SO2, or C=O; X24is C or N; X25is C(R10)2, NR10, SO2, or C=O; R1aand R1bis each independently H, C1-6 alkyl or C1-6 heteroalkyl; R2aand R2bis each independently H, C1-6 alkyl, C1-6 haloalkyl, C3-8cycloalkyl, or C3-8 heterocyclic; R3is H, C1-6 alkyl, or C1-6 heteroalkyl; or R1a, R1b, and R3are taken together with their intervening atoms to form a cyclic group selected from a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring; R4is C1-6 alkyl, C2-6 alkenyl, C1-6 haloalkyl, C1-6 heteroalkyl, C3-8 cycloalkyl, C3-8 heterocycloalkyl, aryl, heteroaryl, -O(RA), -N(RB)(RC), C(=O)(C1-6alkyl), -C(=O)O(C1-6alkyl), - C(=O)(cycloalkyl), -C(=O)(heterocyclic), or -C(=O)(heteroaryl), wherein alkyl, alkenyl, haloalkyl, heteroalkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl are optionally further substituted with 1-6 R11; R5is C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C1-6 heteroalkyl, C3-8 cycloalkyl, C3-8 heterocyclic, aryl, heteroaryl, halogen, cyano, -O(RA), -N(RB)(RC), C(=O)(C1-6alkyl), - C(=O)O(C1-6alkyl), -C(=O)(cycloalkyl), -C(=O)(heterocyclic), or -C(=O)(heteroaryl), wherein alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl are optionally further substituted with 1-6 R11; R6and R7are each independently H, D, C1-6 alkyl, C2-6 alkenyl, C1-6 heteroalkyl, C1-6 haloalkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, halogen, cyano, -O(RA), or -N(RB)(RC), wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclic, aryl, and heteroaryl is optionally substituted with one or more R12; R8aand R8bare each independently H or C1-6 alkyl; or R8aand R8bare taken together with their intervening atoms to an oxo group; R9is H or C1-6 alkyl; R10is H, C1-6 alkyl, C1-6 heteroalkyl, C1-6 haloalkyl, halogen, cyano, -O(RA), -N(RB)(RC), or -N(RB); R11and R12are each independently H, D, C1-6 alkyl, C1-6 heteroalkyl, C1-6 haloalkyl, halogen, oxo, -O(RA), or -N(RB)(RC); each RAis independently H, D, C1-6 alkyl, C1-6 heteroalkyl, C1-6 haloalkyl, cycloalkyl, heterocyclic, or -N(RB)(RC); each RBand RCis independently H, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, cycloalkyl, heterocyclic, or -C(O)-alkyl; R13is an optionally substituted C1-6 aliphatic group,halogen, -OR, -CN, -NR2, -C(=O)R, -C(=O)OR, -C(=O)NR2, -SO2R, -SO2NR2, C1- 6haloalkyl, or C1-6haloalkoxy; n is 0, 1, or 2; and m is 0, 1, or 2 BRIEF DESCRIPTION OF THE DRAWING The drawing shows embodiments of the disclosed subject matter for the purpose of illustrating the invention. However, it should be understood that the present application is not limited to the precise arrangements and embodiments shown in the drawings. FIG.1 shows that soluble TREM2 levels in the cerebrospinal fluid of patients were observed in patients in a single ascending dose study administered a compound of Formula (I) disclosed herein. FIG.2 provides the soluble TREM2 levels in the cerebrospinal fluid of patients in a multiple ascending dose (MAD) study administered a placebo or a compound of Formula (I) disclosed herein at 6 mg, 12 mg, 25 mg, or 50 mg once daily for 14 days. The x-axis is the days after the first dose, so day 0 on the graph is the subject’s sTREM2 levels prior to administration of the first dose. FIG.3 provides the dose-dependent pharmacokinetic (PK) profile of a compound of Formula (I) disclosed herein in the cerebrospinal fluid of healthy volunteers (HV) and patients with Alzheimer’s Diseases (AD) over 24 hours. Healthy volunteers were administered the compound of Formula (I) disclosed herein at a single dose of 2 mg, 6 mg, 18 mg, 36 mg, 72 mg, and 140 mg. One cohort of patients with Alzheimer’s Disease (AD) was administered a single dose of a compound of Formula (I) disclosed herein at 72 mg. FIG.4 provides a side by side comparison of of the PK profiles of the HV and AD cohorts administered 72 mg reported in FIG.3. FIG.5 provides the soluble TREM2 (sTREM2) levels in the cerebrospinal fluid of healthy volunteers and patients with AD in a single ascending dose (SAD) study administered a placebo or a compound of Formula (I) disclosed herein at 6 mg, 18 mg, 36 mg, 72 mg, or 140 mg for 7 days after a single dose.. “a” indicates CSF was not collected from the 2 mg SAD cohort; “b”indicates n=12 at day 7; and “c” indicates the CSF was not collected at day 7. FIG.6 shows the change in concentration of a compound of Formula (I) disclosed herein in the cerebrospinal fluid of healthy volunteers (HV) up to 432 hours in a MAD dose-dependent pharmacokinetics study upon the administration of the first dose of the compound of Formula (I) disclosed herein. Four MAD cohorts of healthy volunteers were administered the compound of Formula (I) disclosed herein daily at 6 mg, 12 mg, 25 mg, or 50 mg. One MAD cohort of elder healthy volunteers was administered the compound of Formula (I) daily at 25 mg. “a” indicates n=5 for time points after 48 hours. FIG.7 provides the soluble TREM2 (sTREM2) levels in the cerebrospinal fluid of healthy volunteers in a multiple ascending dose (MAD) study administered daily a placebo or a compound of Formula (I) disclosed herein at 6 mg, 12 mg, 25 mg, or 50 mg for 14 days, and an elder cohort of healthy volunteers administered daily the compound of Formula (I) disclosed herein at 25 mg for 14 days. FIG.8 provides the pharmacodynamics results of CSF exposure-response modeling. DETAILED DESCRIPTION OF THE INVENTION The disclosure is directed to methods of treating Alzheimer’s Disease in a subject in need thereof, the method comprising administering to the subject a dosage of about 0.5 mg to about 400 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. In some embodiments of the methods described herein, the subject has a mutation in TREM2. In some embodiments of the methods described herein, the subject has one or more of R47H, R62H, H157Y, D87N, T96K, or L211P variants of TREM2. In some embodiments of the methods described herein, the subject has one or more microglia-associated Alzheimer’s Disease risk gene variants. In some embodiments of the methods described herein, the one or more microglia-associated Alzheimer’s Disease risk gene variants is APOE4, MS4A, CD33, CLU, INPPSD, or CR1. In some embodiments of the methods described herein, the subject has been identified and / or diagnosed as having Alzheimer’s Disease. In some embodiments of the methods described herein, the subject has a diagnosis of mild cognitive impairment due to Alzheimer’s Disease. In some embodiments of the methods described herein, the subject has a diagnosis of mild Alzheimer’s Disease according to the 2018 National Institutes on Aging and Alzheimer’s Association criteria. In some embodiments of the methods described herein, the subject has a MMSE score of 18 to 30 (inclusive). In some embodiments of the methods described herein, the subject is asymptomatic for Alzheimer’s Disease. In some embodiments of the methods described herein, the small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof is administered to the subject prior to the onset of signs or symptoms of Alzheimer’s Disease. In some embodiments of the methods described herein, the subject is aged 18 years or older. In some embodiments of the methods described herein, after being administered a compound of Formula (I) described herein once daily for 14 days, the subject exhibits at least a 10% decrease in the concentrations of soluble TREM2 (sTREM2) in the CSF as compared with the sTREM2 levels prior to administration of the compound. In some embodiments of the methods described herein, after being administered a compound of Formula (I) once daily for 14 days, the subject exhibits at least a 10%, at least a 15%, at least a 20%, at least a 25%, at least a 30%, at least a 35%, at least a 40%, at least a 45%, at least a 50%, at least a 55% decrease, or at least a 60% decrease in the concentrations of sTREM2 in the CSF as compared with the levels prior to administration of the compound. In some embodiments of the methods described herein, the subject exhibits at least a 50% decrease in the concentrations of sTREM2 in the CSF after administration of a compound of Formula (I) described herein, e.g., as compared with the levels prior to administration of the compound. In some embodiments of the methods described herein, after being administered a compound of Formula (I) described herein once daily for 14 days, the subject exhibits a 70% decrease in the concentrations of soluble TREM2 (sTREM2) in the CSF as compared with the levels prior to administration of the compound. In some embodiments of the methods described herein, after being administered a compound of Formula (I) described herein once daily for 14 days, the subject exhibits a 70%, a 65%, a 60%, a 55%, a 50%, a 45%, a 40%, a 35%, a 30%, a 25%, a 20%, a 15%, or a 10% decrease in the concentrations of sTREM2 in the CSF e.g., as compared with the levels prior to administration of the compound. Definitions The following definitions are provided to assist in understanding the scope of this disclosure. Unless otherwise indicated, all numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification or claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the standard deviation found in their respective testing measurements. As used herein, if any variable occurs more than one time in a chemical formula, its definition on each occurrence is independent of its definition at every other occurrence. If the chemical structure and chemical name conflict, the chemical structure is determinative of the identity of the compound. As used herein, the following definitions shall apply unless otherwise indicated. For purposes of this disclosure, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 101stEd. Additionally, general principles of organic chemistry are described in “Organic Chemistry”, Thomas Sorrell, University Science Books, Sausalito: 2005, and “March’s Advanced Organic Chemistry: Reactions Mechanisms and Structure”, 8thEd., Ed.: Smith, M.B., John Wiley & Sons, New York: 2019, the entire contents of which are hereby incorporated by reference. Stereoisomers The compounds of the present disclosure may contain, for example, double bonds, one or more asymmetric carbon atoms, and bonds with a hindered rotation, and therefore, may exist as stereoisomers, such as double-bond isomers (i.e., geometric isomers (E / Z)), enantiomers, diastereomers, and atropoisomers. Accordingly, the scope of the instant disclosure is to be understood to encompass all possible stereoisomers of the illustrated compounds, including the stereoisomerically pure form (for example, geometrically pure, enantiomerically pure, diastereomerically pure, and atropoisomerically pure) and stereoisomeric mixtures (for example, mixtures of geometric isomers, enantiomers, diastereomers, and atropoisomers, or mixture of any of the foregoing) of any chemical structures disclosed herein (in whole or in part), unless the stereochemistry is specifically identified. If the stereochemistry of a structure or a portion of a structure is not indicated with, for example, bold or dashed lines, the structure or portion of the structure is to be interpreted as encompassing all stereoisomers of it. If the stereochemistry of a structure or a portion of a structure is indicated with, for example, bold or dashed lines, the structure or portion of the structure is to be interpreted as encompassing only the stereoisomer indicated. For example, (1R)-1-methyl-2-(trifluoromethyl)cyclohexane is meant to encompass (1R,2R)-1-methyl-2- (trifluoromethyl)cyclohexane and (1R,2S)-1-methyl-2-(trifluoromethyl)cyclohexane. A bond drawn with a wavy line indicates that both stereoisomers are encompassed. This is not to be confused with a wavy line drawn perpendicular to a bond which indicates the point of attachment of a group to the rest of the molecule. The term “stereoisomer” or “stereoisomerically pure” compound as used herein refers to one stereoisomer (for example, geometric isomer, enantiomer, diastereomer and atropoisomer) of a compound that is substantially free of other stereoisomers of that compound. For example, a stereoisomerically pure compound having one chiral center will be substantially free of the mirror image enantiomer of the compound and a stereoisomerically pure compound having two chiral centers will be substantially free of the other enantiomer and diastereomers of the compound. A typical stereoisomerically pure compound comprises greater than about 80% by weight of one stereoisomer of the compound and equal or less than about 20% by weight of other stereoisomers of the compound, greater than about 90% by weight of one stereoisomer of the compound and equal or less than about 10% by weight of the other stereoisomers of the compound, greater than about 95% by weight of one stereoisomer of the compound and equal or less than about 5% by weight of the other stereoisomers of the compound, or greater than about 97% by weight of one stereoisomer of the compound and equal or less than about 3% by weight of the other stereoisomers of the compound. This disclosure also encompasses the pharmaceutical compositions comprising stereoisomerically pure forms and the use of stereoisomerically pure forms of any compounds disclosed herein. Further, this disclosure also encompasses pharmaceutical compositions comprising mixtures of stereoisomers of any compounds disclosed herein and the use of the pharmaceutical compositions or mixtures of stereoisomers. These stereoisomers or mixtures thereof may be synthesized in accordance with methods well known in the art and methods disclosed herein. Mixtures of stereoisomers may be resolved using standard techniques, such as chiral columns or chiral resolving agents. See, for example, Jacques et al., Enantiomers, Racemates and Resolutions (Wiley-Interscience, New York, 1981); Wilen et al., Tetrahedron 33:2725; Eliel, Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); and Wilen, Tables of Resolving Agents and Optical Resolutions, page 268 (Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN, 1972). Tautomers As known by those skilled in the art, certain compounds disclosed herein may exist in one or more tautomeric forms. Because one chemical structure may only be used to represent one tautomeric form, it will be understood that for convenience, referral to a compound of a given structural Formula (I) includes other tautomers of the structural formula. Accordingly, the scope of the instant disclosure is to be understood to encompass all tautomeric forms of the compounds disclosed herein. Isotopically-Labelled Compounds Further, the scope of the present disclosure includes all pharmaceutically acceptable isotopically-labelled compounds of the compounds disclosed herein, such as the compounds of Formula (I), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein one or more atoms are replaced by atoms having the same atomic number, but an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes suitable for inclusion in the compounds disclosed herein include isotopes of hydrogen, such as2H and3H, carbon, such as11C,13C and14C, chlorine, such as36Cl, fluorine, such as18F, iodine, such as123I and125I, nitrogen, such as13N and15N, oxygen, such as15O,17O, and18O, phosphorus, such as32P, and sulphur, such as35S. Certain isotopically-labelled compounds of Formula (I), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, for example, those incorporating a radioactive isotope, are useful in drug and / or substrate tissue distribution studies. The radioactive isotopes tritium (3H) and carbon-14 (14C) are particularly useful for this purpose in view of their ease of incorporation and ready means of detection. Substitution with isotopes such as deuterium (2H or D) may afford certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements, and hence may be advantageous in some circumstances. Substitution with positron emitting isotopes, such as11C,18F,15O and13N, can be useful in Positron Emission Topography (PET) studies, for example, for examining target occupancy. Isotopically-labelled compounds of the compounds disclosed herein can generally be prepared by conventional techniques known to those skilled in the art or by processes analogous to those described in the accompanying General Synthetic Schemes and Examples using an appropriate isotopically-labelled reagent in place of the non-labelled reagent previously employed. Solvates As discussed above, the compounds disclosed herein and the stereoisomers, tautomers, and isotopically-labelled forms thereof or a pharmaceutically acceptable salt of any of the foregoing may exist in solvated or unsolvated forms. The term “solvate” as used herein refers to a molecular complex comprising a compound or a pharmaceutically acceptable salt thereof as described herein and a stoichiometric or non- stoichiometric amount of one or more pharmaceutically acceptable solvent molecules. If the solvent is water, the solvate is referred to as a “hydrate.” Accordingly, the scope of the instant disclosure is to be understood to encompass all solvents of the compounds disclosed herein and the stereoisomers, tautomers and isotopically- labelled forms thereof or a pharmaceutically acceptable salt of any of the foregoing. Miscellaneous Definitions This section will define additional terms used to describe the scope of the compounds, compositions and uses disclosed herein. The term “small molecule TREM2 agonist” refers to a small molecule that exhibits agonism of TREM2. The term “about” will be understood by persons of ordinary skill in the art and will vary to some extent on the context in which it is used. As used herein when referring to a measurable value such as an amount, a temporal duration, and the like, the term “about” is meant to encompass variations of ±10%. The terms “C1-3 alkyl,” “C1-5 alkyl,” and “C1-6 alkyl” as used herein refer to a straight or branched chain hydrocarbon containing from 1 to 3, 1 to 5, and 1 to 6 carbon atoms, respectively. Representative examples of C1-3 alkyl, C1-5 alky, or C1-6 alkyl include, but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, pentyl and hexyl. The term “C2-4 alkenyl” as used herein refers to a saturated hydrocarbon containing 2 to 4 carbon atoms having at least one carbon-carbon double bond. Alkenyl groups include both straight and branched moieties. Representative examples of C2-4 alkenyl include, but are not limited to, 1-propenyl, 2-propenyl, 2-methyl-2-propenyl, and butenyl. The term “C3-8 cycloalkyl” as used herein refers to a saturated carbocyclic molecule wherein the cyclic framework has 3 to 8 carbon atoms. Representative examples of C38 cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. The terms “diC1-3alkylamino” as used herein refer to –NR*R**, wherein R* and R** independently represent a C1-3 alkyl as defined herein. Representative examples of diC1- 3alkylamino include, but are not limited to, -N(CH3)2, -N(CH2CH3)2, -N(CH3)(CH2CH3), - N(CH2CH2CH3)2, and –N(CH(CH3)2)2. The term “C1-3 alkoxy” and “C1-6 alkoxy” as used herein refer to –OR#, wherein R#represents a C1-3 alkyl and C1-6 alkyl group, respectively, as defined herein. Representative examples of C1-3 alkoxy or C1-6 alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, iso-propoxy, and butoxy. The term “halogen” as used herein refers to –F, -CI, -Br, or -I. The term “halo” as used herein as a prefix to another term for a chemical group refers to a modification of the chemical group, wherein one or more hydrogen atoms are substituted with a halogen as defined herein. The halogen is independently selected at each occurrence. For example, the term “C1-6 haloalkyl” refers to a C1-6 alkyl as defined herein, wherein one or more hydrogen atoms are substituted with a halogen. Representative examples of C1-6 haloalkyl include, but are not limited to, -CH2F, -CHF2, -CF3, -CHFCl, -CH2CF3, -CFHCF3, -CF2CF3, - CH(CF3)2, -CF(CHF2)2, and -CH(CH2F)(CF3). Further, the term “C1-6 haloalkoxy” for example refers to a C1-6 alkoxy as defined herein, wherein one or more hydrogen atoms are substituted with a halogen. Representative examples of C1-6 haloalkoxy include, but are not limited to, - OCH2F, -OCHF2, -OCF3, -OCHFCl, -OCH2CF3, -OCFHCF3, -OCF2CF3, -OCH(CF3)2, - OCF(CHF2)2, and -OCH(CH2F)(CF3). The term “5-membered heteroaryl” or “6-membered heteroaryl” as used herein refers to a 5 or 6-membered carbon ring with two or three double bonds containing one ring heteroatom selected from N, S, and O and optionally one or two further ring N atoms instead of the one or more ring carbon atom(s). Representative examples of a 5-membered heteroaryl include, but are not limited to, furyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, and oxazolyl. Representative examples of a 6-membered heteroaryl include, but are not limited to, pyridyl, pyrimidyl, pyrazyl, and pyridazyl. The term “C1-6 heteroalkyl” as used herein refers to a straight or branched chain hydrocarbon containing from 1 to 6 carbon atoms and wherein one carbon atom is substituted with a heteroatom selected from N, O, and S, wherein the N, O, and S atoms my be further substituted by hydrogen or a C1-3 alkyl group. Representative examples of C1-6 heteroalkyl include, but are not limited to -CH2NH2, -(CH2)2NH2, -(CH2)3NH2, -(CH2)4NH2, -(CH2)5NH2, -(CH2)6NH2, - (CH2)2NHCH2, -(CH2)2NH(CH2)2, -CH2OH, -(CH2)2OH, -(CH2)3OH, -(CH2)4OH, -(CH2)5OH, - (CH2)6OH, -(CH2)2OCH2, -(CH2)2O(CH2)2, -CH2SH, -(CH2)2SH, -(CH2)3SH, -(CH2)4SH, - (CH2)5SH, -(CH2)6SH, -(CH2)2SCH2, and -(CH2)2S(CH2)2. The term “C3-6 heterocycloalkyl” as used herein refers to a saturated carbocyclic molecule wherein the cyclic framework has 3 to 6 carbons and wherein one carbon atom is substituted with a heteroatom selected from N, O, and S. If the C3-6 heterocycloalkyl group is a C6 heterocycloalkyl, one or two carbon atoms are substituted with a heteroatom independently selected from N, O, and S. Representative examples of C3-6 heterocycloalkyl include, but are not limited to, aziridinyl, azetidinyl, oxetanyl, pyrrolidinyl, piperazinyl, morpholinyl, and thiomorpholinyl. The term “C5-8spiroalkyl” as used herein refers a bicyclic ring system, wherein the two rings are connected through a single common carbon atom. Representative examples of C5-8 spiroalkyl include, but are not limited to, spiro[2.2]pentanyl, spiro[3.2]hexanyl, spiro[3.3]heptanyl, spiro[3.4]octanyl, and spiro[2.5]octanyl. The term “C5-8 tricycloalkyl” as used herein refers a tricyclic ring system, wherein all three cycloalkyl rings share the same two ring atoms. Representative examples of C5-8 tricycloalkyl include, but are not limited to, tricyclo[1.1.1.01,3]pentanyl, , tricyclo[2.1.1.01,4]hexanyl, tricyclo[3.1.1.01,5]hexanyl, and tricyclo[3.2.1.01,5]octanyl. The term “aryl” used alone or as part of a larger moiety as in “aralkyl,” “aralkoxy,” or “aryloxyalkyl,” refers to monocyclic or bicyclic ring systems having a total of 4 to 14 ring members, wherein at least one ring in the system is aromatic and wherein each ring in the system contains three to seven ring members. The term “aryl” may be used interchangeably with the term “aryl ring”. In certain embodiments of the present disclosure, “aryl” refers to an aromatic ring system which includes, but not limited to, phenyl, biphenyl, naphthyl, anthracyl and the like, which may bear one or more substituents. Also included within the scope of the term “aryl,” as it is used herein, is a group in which an aromatic ring is fused to one or more non–aromatic rings, such as indanyl, phthalimidyl, naphthimidyl, phenanthridinyl, or tetrahydronaphthyl, and the like. The terms “heteroaryl” and “heteroar–,” used alone or as part of a larger moiety, e.g., “heteroaralkyl,” or “heteroaralkoxy,” refer to groups having 5 to 10 ring atoms, preferably 5, 6, or 9 ring atoms; having 6, 10, or 14 π electrons shared in a cyclic array; and having, in addition to carbon atoms, from one to five heteroatoms. The term “heteroatom” in the context of “heteroaryl” particularly includes, but is not limited to, nitrogen, oxygen, or sulfur, and includes any oxidized form of nitrogen or sulfur, and any quaternized form of a basic nitrogen. Heteroaryl groups include, without limitation, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, purinyl, naphthyridinyl, and pteridinyl. The terms “heteroaryl” and “heteroar–”, as used herein, also include groups in which a heteroaromatic ring is fused to one or more aryl, cycloaliphatic, or heterocyclyl rings, where the radical or point of attachment is on the heteroaromatic ring. Nonlimiting examples include indolyl, isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzthiazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H– quinolizinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and pyrido[2,3–b]–1,4–oxazin–3(4H)–one. A heteroaryl group may be monocyclic or bicyclic. A heteroaryl ring may include one or more oxo (=O) or thioxo (=S) substituent. The term “heteroaryl” may be used interchangeably with the terms “heteroaryl ring,” “heteroaryl group,” or “heteroaromatic,” any of which terms include rings that are optionally substituted. The term “heteroaralkyl” refers to an alkyl group substituted by a heteroaryl, wherein the alkyl and heteroaryl portions independently are optionally substituted. As described herein, compounds of the present disclosure may contain “substituted” moieties. In general, the term “substituted” means that one or more hydrogens of the designated moiety are replaced with a suitable substituent. Unless otherwise indicated, an “optionally substituted” group may have a suitable substituent at one or more substitutable position of the group, and when more than one position in any given structure is substituted with more than one substituent selected from a specified group, the substituent may be either the same or different at every position. Combinations of substituents envisioned by the present disclosure are preferably those that result in the formation of stable or chemically feasible compounds. The term “stable,” as used herein, refers to compounds that are not substantially altered when subjected to conditions to allow for their production, detection, and, in certain embodiments, their recovery, purification, and use for one or more of the purposes disclosed herein. The term “pharmaceutically acceptable” as used herein refers to generally recognized for use in subjects, particularly in humans. The term “pharmaceutically acceptable salt” as used herein refers to a salt of a compound that is pharmaceutically acceptable and that possesses the desired pharmacological activity of the parent compound. Such salts include: (1) acid addition salts, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or formed with organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4- hydroxybenzoyl) benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, and the like; or (2) salts formed when an acidic proton present in the parent compound either is replaced by a metal ion, for example, an alkali metal ion, an alkaline earth ion, or an aluminum ion; or coordinates with an organic base such as ethanolamine, diethanolamine, triethanolamine, N- methylglucamine, dicyclohexylamine, and the like. Additional examples of such salts can be found in Berge et al., J. Pharm. Sci.66(1):1-19 (1977). See also Stahl et al., Pharmaceutical Salts: Properties, Selection, and Use, 2ndRevised Edition (2011). The term “pharmaceutically acceptable excipient” as used herein refers to a broad range of ingredients that may be combined with a compound or salt disclosed herein to prepare a pharmaceutical composition or formulation. Typically, excipients include, but are not limited to, diluents, colorants, vehicles, anti-adherants, glidants, disintegrants, flavoring agents, coatings, binders, sweeteners, lubricants, sorbents, preservatives, and the like. The term “subject” as used herein refers to humans and mammals, including, but not limited to, primates, cows, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In one embodiment the subject is a human. Compounds Useful in the Compositions and Methods of the Disclosure The present disclosure features compositions and methods for the administration of a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (I) has the following structure: or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein Ring A together with the 6-membered ring system to which it is fused forms a bicyclic ring system selected from: wherein X1is CR10or N; X2is C(R10)2, O, C(=O), S(O)2, or NR10; X3is CR10or N; X4is CR10or N; X5is CR10or N; X6is CR10, N, or NR10; X7is CR10or N; X8is CR10or N; X9is CR10or N; X10is CR10, C(R10)2, O, S or NR10; X11is C or N; X12is CR10or NR10; X13is C or N; X23is CR10, N, NR10, SO2, or C=O; X24is CR10, N, NR10, SO2, or C=O; X25is CR10, N, NR10, SO2, or C=O; L is a bond or an optionally substituted straight chain or branched C1-6 alkylene; wherein the straight chain or branched C1-6 alkylene is optionally substituted with C1-6 alkyl, hydroxyl, or -N(RB)(RC); R1aand R1bis each independently H, C1-6 alkyl, or C1-6 heteroalkyl; R2aand R2bis each independently H, D, C1-6 alkyl, C1-6 haloalkyl, C1-6 heteroalkyl, C3- 8cycloalkyl, or C3-8 heterocyclic; R3is H, D, C1-6 alkyl, or C1-6 heteroalkyl; or R1a, R1b, and R3are taken together with their intervening atoms to form a cyclic group selected from a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring; R4is C1-6 alkyl, C2-6 alkenyl, C1-6 haloalkyl, C1-6 heteroalkyl, C3-8 cycloalkyl, C3-8 heterocycloalkyl, aryl, heteroaryl, -O(RA), -N(RB)(RC), C(=O)(C1-6alkyl), -C(=O)O(C1-6alkyl), - C(=O)(cycloalkyl), -C(=O)(heterocyclic), or -C(=O)(heteroaryl), wherein alkyl, alkenyl, haloalkyl, heteroalkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl are optionally further substituted with 1-6 R11; R5is C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C1-6 heteroalkyl, C3-8 cycloalkyl, C3-8 heterocyclic, aryl, heteroaryl, halogen, cyano, -O(RA), -N(RB)(RC), C(=O)(C1-6alkyl), - C(=O)O(C1-6alkyl), -C(=O)(cycloalkyl), -C(=O)(heterocyclic), or -C(=O)(heteroaryl), wherein alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl are optionally further substituted with 1-6 R11; R6and R7are each independently H, D, C1-6 alkyl, C2-6 alkenyl, C1-6 heteroalkyl, C1-6 haloalkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, halogen, cyano, -O(RA), or -N(RB)(RC), wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclic, aryl, and heteroaryl is optionally substituted with one or more R12; or wherein the R6and R7groups together with the carbons to which they are attached form a 5- membered heterocyclic group. R8aand R8bare each independently H or C1-6 alkyl; or R8aand R8bare taken together with their intervening atoms to an oxo group; R9is H or C1-6 alkyl; R10is H, C1-6 alkyl, C1-6 heteroalkyl, C1-6 haloalkyl, heteroaryl, halogen, cyano, - O(RA), -N(RB)(RC), or -N(RB), wherein heteroaryl is optionally further substituted with 1-6 R11, or wherein any two R10groups together with the carbons to which they are attached at X23, X24, or X25form a 5-membered heterocyclic group; R11and R12are each independently H, D, C1-6 alkyl, C1-6 heteroalkyl, C1-6 haloalkyl, halogen, oxo, -O(RA), or -N(RB)(RC); each RAis independently H, D, C1-6 alkyl, C1-6 heteroalkyl, C1-6 haloalkyl, cycloalkyl, heterocyclic, or -N(RB)(RC); each RBand RCis independently H, C1-6 alkyl, C1-6 heteroalkyl, C1-6 heteroaralkyl, C1-6 haloalkyl, cycloalkyl, heterocyclic, or -C(O)-alkyl, wherein the C1-6 alkyl or heterocyclic is optionally further substituted with cycloalkyl or –O(RA); R13is an optionally substituted C1-6 aliphatic group, halogen, -OR, -CN, -NR2, -C(=O)R, -C(=O)OR, -C(=O)NR2, -SO2R, -SO2NR2, C1-6haloalkyl, or C1-6haloalkoxy; n is 0, 1, or 2; and m is 0, 1, or 2. In some embodiments, the compound of Formula (I), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer has: Ring A together with the 6-membered ring system to which it is fused forms a bicyclic ring system selected from:

[0004] Ring B is selected from: wherein X1is CR10or N; X2is C(R10)2, O, C(=O), S(O)2, or NR10; X3is CR10or N; X4is CR10or N; X5is CR10or N; X6is CR10or NR10; X7is CR10or N; X8is CR10or N; X9is CR10or N; X10is C(R10)2, O, S or NR10; X11is C or N; X12is CR10or NR10; X13is C or N; X23is C(R10)2, NR10, SO2, or C=O; X24is C or N; X25is C(R10)2, NR10, SO2, or C=O; R1aand R1bis each independently H, C1-6 alkyl or C1-6 heteroalkyl; R2aand R2bis each independently H, C1-6 alkyl, C1-6 haloalkyl, C3-8cycloalkyl, or C3-8 heterocyclic; R3is H, C1-6 alkyl, or C1-6 heteroalkyl; or R1a, R1b, and R3are taken together with their intervening atoms to form a cyclic group selected from a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring; R4is C1-6 alkyl, C2-6 alkenyl, C1-6 haloalkyl, C1-6 heteroalkyl, C3-8 cycloalkyl, C3-8 heterocycloalkyl, aryl, heteroaryl, -O(RA), -N(RB)(RC), C(=O)(C1-6alkyl), -C(=O)O(C1-6alkyl), - C(=O)(cycloalkyl), -C(=O)(heterocyclic), or -C(=O)(heteroaryl), wherein alkyl, alkenyl, haloalkyl, heteroalkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl are optionally further substituted with 1-6 R11; R5is C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C1-6 heteroalkyl, C3-8 cycloalkyl, C3-8 heterocyclic, aryl, heteroaryl, halogen, cyano, -O(RA), -N(RB)(RC), C(=O)(C1-6alkyl), - C(=O)O(C1-6alkyl), -C(=O)(cycloalkyl), -C(=O)(heterocyclic), or -C(=O)(heteroaryl), wherein alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl are optionally further substituted with 1-6 R11; R6and R7are each independently H, D, C1-6 alkyl, C2-6 alkenyl, C1-6 heteroalkyl, C1-6 haloalkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, halogen, cyano, -O(RA), or -N(RB)(RC), wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclic, aryl, and heteroaryl is optionally substituted with one or more R12; R8aand R8bare each independently H or C1-6 alkyl; or R8aand R8bare taken together with their intervening atoms to an oxo group; R9is H or C1-6 alkyl; R10is H, C1-6 alkyl, C1-6 heteroalkyl, C1-6 haloalkyl, halogen, cyano, -O(RA), -N(RB)(RC), or -N(RB); R11and R12are each independently H, D, C1-6 alkyl, C1-6 heteroalkyl, C1-6 haloalkyl, halogen, oxo, -O(RA), or -N(RB)(RC); each RAis independently H, D, C1-6 alkyl, C1-6 heteroalkyl, C1-6 haloalkyl, cycloalkyl, heterocyclic, or -N(RB)(RC); each RBand RCis independently H, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, cycloalkyl, heterocyclic, or -C(O)-alkyl; R13is an optionally substituted C1-6 aliphatic group, halogen, -OR, -CN, -NR2, -C(=O)R, -C(=O)OR, -C(=O)NR2, -SO2R, -SO2NR2, C1-6haloalkyl, or C1-6haloalkoxy; n is 0, 1, or 2; and m is 0, 1, or 2. Suitable compounds for the methods and uses provided herein include compounds of Formula (II): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above. In some embodiments, the small molecule TREM2 agonist is a compound of Formula (II): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein X1is CR10or N; X2is C(R10)2 or O; R2aand R2bis each independently H, D, methyl, , , ; R3is H or D; R6is H, methyl, propyl, R7is methyl, Suitable compounds for the methods and uses provided herein include compounds of Formula (IIA): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (II). Suitable compounds for the methods and uses provided herein include compounds of Formula (IIB): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (II). Suitable compounds for the methods and uses provided herein include compounds of Formula (IIC): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (II). Suitable compounds for the methods and uses provided herein include compounds of Formula (IID): tautomer thereof, or a pharmaceutically a le salt of the compound or the tautomer, wherein each variable is as defined above for Formula (II). Suitable compounds for the methods and uses provided herein include compounds of Formula (IIE): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (II). Suitable compounds for the methods and uses provided herein include compounds of Formula (III): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above. In some embodiments, the small molecule TREM2 agonist is a compound of Formula (III): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein X1is CR10or N; X2is C(R10)2 or O; R2aand R2bis each independently H or methyl; R3is H; R6is H; and R7is methyl. Suitable compounds for the methods and uses provided herein include compounds of Formula (IIIA): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (III). Suitable compounds for the methods and uses provided herein include compounds of Formula (IIIB): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (III). Suitable compounds for the methods and uses provided herein include compounds of Formula (IIIC): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (III). Suitable compounds for the methods and uses provided herein include compounds of Formula (IIID): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (III). Suitable compounds for the methods and uses provided herein include compounds of Formula (IIIE): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (III). Suitable compounds for the methods and uses provided herein include compounds of Formula (IV): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above. In some embodiments, the small molecule TREM2 agonist is a compound of Formula (IV): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein X1is CR10or N; X2is C(R10)2 or O; R2aand R2bis each independently H; R3is H; R7methyl; or wherein the R6and R7groups together with the carbons to which they are attached form a 5- membered heterocyclic group. In some embodiments, the 5-membered heterocyclic group is . Suitable compounds for the methods and uses provided herein include compounds of Formula (IVA): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (IV). Suitable compounds for the methods and uses provided herein include compounds of Formula (IVB): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (IV). Suitable compounds for the methods and uses provided herein include compounds of Formula (IVC): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (IV). Suitable compounds for the methods and uses provided herein include compounds of Formula (IVD): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (IV). Suitable compounds for the methods and uses provided herein include compounds of Formula (IVE): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (IV). Suitable compounds for the methods and uses provided herein include compounds of Formula (V): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above. In some embodiments, the small molecule TREM2 agonist is a compound of Formula (V): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein X4is N; X5is CR10; X6is CR10or N; X23is CR10or C=O; X24is CR10or N; X25is CR10, N, or NR10; , R6is H, Cl, or methyl; R7is methyl or Cl; and , any two R10groups together with the carbons to which they are attached at X23, X24, or X25form a 5-membered heterocyclic group. In some embodiments, the 5-membered heterocycloalkyl group is . Suitable compounds for the methods and uses provided herein include compounds of Formula (VI): (VI), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above. In some embodiments, the small molecule TREM2 agonist is a compound of Formula (VI): (VI), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein X1is CR10; X2is O; X4is N; X5is CR10; X6is CR10; X13is C: R2aand R2bis each independently H; R3is H; R10is H. Suitable compounds for the methods and uses provided herein include compounds of Formula (VII): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above. In some embodiments, the small molecule TREM2 agonist is a compound of Formula (VII): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein X4is N; X10is S; X23is CR10; X24is CR10; X25is CR10; R7is methyl; and . Suitable compounds for the methods and uses provided herein include compounds of Formula (VIII): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above. In some embodiments, the small molecule TREM2 agonist is a compound of Formula (VIII): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein X4is N; X10is S; X23is CR10; X24is CR10; X25is CR10; L is a bond or an optionally substituted straight chain or branched C1-6 alkylene; wherein the straight chain or branched C1-6 alkylene is optionally substituted with methyl, or R7is methyl, NH2, , , ; R10is H, Cl, or Suitable compounds for the methods and uses provided herein include compounds of Formula (IX): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above. In some embodiments, the small molecule TREM2 agonist is a compound of Formula (IX): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein X1is CR10; X2is O: X3is N; X4is CR10; X6is N; R2aand R2bis each independently H; R3is H; R6is methyl; R7is methyl; and R10is H. Suitable compounds for the methods and uses provided herein include compounds of Formula (X): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above. In some embodiments, the small molecule TREM2 agonist is a compound of Formula (X): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein X1is CR10or N; X2is O; X3is CR10or N; X4is CR10or N: X5is CR10or N; R2aand R2bis each independently H or methyl; R3is H; R7is methyl; and R10is H or methyl; Suitable compounds for the methods and uses provided herein include compounds of Formula (XA): (XA), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (X). Suitable compounds for the methods and uses provided herein include compounds of Formula (XB): (XB), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (X). Suitable compounds for the methods and uses provided herein include compounds of Formula (XC): (XC), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (X). Suitable compounds for the methods and uses provided herein include compounds of Formula (XD): (XD), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (X). Suitable compounds for the methods and uses provided herein include compounds of Formula (XE): (XE), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (X). Suitable compounds for the methods and uses provided herein include compounds of Formula (XI): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above. In some embodiments, the small molecule TREM2 agonist is a compound of Formula (XI): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein X1is CR10or N; X2is O; X3is CR10or N; X4is CR10or N: X5is CR10; R2aand R2bis each independently H, methyl, or cyclopropyl; R3is H; R7is H, methyl, ethyl, or cyclopropyl; and R10is H. Suitable compounds for the methods and uses provided herein include compounds of Formula (XIA): (XIA), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XI). Suitable compounds for the methods and uses provided herein include compounds of Formula (XIB): (XIB), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XI). Suitable compounds for the methods and uses provided herein include compounds of Formula (XIC): (XIC), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XI). Suitable compounds for the methods and uses provided herein include compounds of Formula (XID): (XID), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XI). Suitable compounds for the methods and uses provided herein include compounds of Formula (XIE): (XIE), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XI). Suitable compounds for the methods and uses provided herein include compounds of Formula (XII): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above. In some embodiments, the small molecule TREM2 agonist is a compound of Formula (XII): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein X2is O; X3is CR10; X4is N; R2aand R2bis each independently H; R3is H; R7methyl. Suitable compounds for the methods and uses provided herein include compounds of Formula (XIII): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above. In some embodiments, the small molecule TREM2 agonist is a compound of Formula (XIII): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein X1is CR10or N; X2is O or C(R10)2; X3is N; X4is N; X6is N; X10is O or S; X12is CR10; R2aand R2bis each independently H or methyl; R3is H; R10is H, F, methyl, , Suitable compounds for the methods and uses provided herein include compounds of Formula (XIIIA): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XIII). Suitable compounds for the methods and uses provided herein include compounds of Formula (XIIIB): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XIII). Suitable compounds for the methods and uses provided herein include compounds of Formula (XIIIC): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XIII). Suitable compounds for the methods and uses provided herein include compounds of Formula (XIIID): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XIII). Suitable compounds for the methods and uses provided herein include compounds of Formula (XIIIE): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XIII). Suitable compounds for the methods and uses provided herein include compounds of formula (XIV): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above. In some embodiments, the small molecule TREM2 agonist is a compound of Formula (XIV): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein X1is N; X2is O; X3is N; X4is N; X6is N; X10is CR10; X12is NR10; R2aand R2bis each independently H or methyl; R3is H; . Suitable compounds for the methods and uses provided herein include compounds of formula (XIVA): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XIV). Suitable compounds for the methods and uses provided herein include compounds of formula (XIVB): (XIVB), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XIV). Suitable compounds for the methods and uses provided herein include compounds of formula (XIVC): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XIV). Suitable compounds for the methods and uses provided herein include compounds of formula (XIVD): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XIV). Suitable compounds for the methods and uses provided herein include compounds of formula (XIVE): (XIVE), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XIV). Suitable compounds for the methods and uses provided herein include compounds of formula (XV): (XV), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above. In some embodiments, the small molecule TREM2 agonist is a compound of Formula (XV), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein Ring B is wherein X1is CR10; X2is C(=O) or S(O)2; X23is CR10or NR10; X24is CR10or NR10; X25is C=O; R2aand R2bis each independently H; R4is R5is R6is methyl; R7is methyl; and R10 is H, methyl, .Suitable compounds for the methods and uses provided herein include compounds of formula (XVI): (XVI), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above. In some embodiments, the small molecule TREM2 agonist is a compound of Formula (XVI): (XVI), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein Ring B is wherein X1is N; X2is O; X23is CR10; X24is CR10; X25is CR10; R2aand R2bis each independently H or methyl; R3is H; R6is methyl; R7is methyl; R10is H or Cl; and R13is F. Suitable compounds for the methods and uses provided herein include compounds of formula (XVII): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above. In some embodiments, the small molecule TREM2 agonist is a compound of Formula (XVII): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein X2is O; R2aand R2bis each independently H; R3is H; R6is methyl; and R7is methyl. Suitable compounds for the methods and uses provided herein include compounds of formula (XVIIA): (XVIIA), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XVII). Suitable compounds for the methods and uses provided herein include compounds of formula (XVIIB): (XVIIB), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XVII). Suitable compounds for the methods and uses provided herein include compounds of formula (XVIIC): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XVII). Suitable compounds for the methods and uses provided herein include compounds of formula (XVIID): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XVII). Suitable compounds for the methods and uses provided herein include compounds of formula (XVIIE): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XVII). Suitable compounds for the methods and uses provided herein include compounds of formula (XVIII): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above. In some embodiments, the small molecule TREM2 agonist is a compound of Formula (XVIII): (XVIII), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein X2is O; R2aand R2bis each independently H; R3is H; R6is H or methyl; and R7is methyl. Suitable compounds for the methods and uses provided herein include compounds of formula (XVIIIA): (XVIIIA), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XVIII). Suitable compounds for the methods and uses provided herein include compounds of formula (XVIIIB): (XVIIIB), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XVIII). Suitable compounds for the methods and uses provided herein include compounds of formula (XVIIIC): (XVIIIC), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XVIII). Suitable compounds for the methods and uses provided herein include compounds of formula (XVIIID): (XVIIID), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XVIII). Suitable compounds for the methods and uses provided herein include compounds of formula (XVIIIE): (XVIIIE), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above for Formula (XVIII). Suitable compounds for the methods and uses provided herein include compounds of formula (XIX): (XIX), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above. In some embodiments, the small molecule TREM2 agonist is a compound of Formula (XIX): (XIX), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein X3is N; X4is CR10; X6is N; X7is N; X23is CR10; X24is CR10; X25is CR10: R6is methyl; R7is methyl; R10is H or F; and R13is F. Suitable compounds for the methods and uses provided herein include compounds of formula (XX): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above. In some embodiments, the small molecule TREM2 agonist is a compound of Formula (XX): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein X1is N; X2is O; X3is N; X4is N; X6is NR10; X10is S; X12is C=NR10; R2aand R2bis each independently H or methyl; R3is H; R10is H, methyl, or ethyl. Suitable compounds for the methods and uses provided herein include a compound selected from Table A, or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer. Particularly preferred compounds for use in the methods of the disclosure are compounds of Formula II, IIA, IIB, IIC, IID, IIE, III, IIIA, IIIB, IIIC, IIID and IIIE. More particularly preferred compounds for use in the methods of the disclosure are compounds of Formula II. Exemplary compounds of Formula (I) are provided in Table A. Table A. Exemplary Compounds

[0005] In some embodiments, the exemplary compounds of the disclosure set forth in Table A, above, exist as the compound or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer. In some embodiments, the compound of Formula (I) is Compound 100 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 101 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 102 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 103 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 104 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 105 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 106 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 107 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 108 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 109 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 110 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 111 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 112 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 113 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 114 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 115 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 116 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 117 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 118 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 119 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 120 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 121 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 122 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 123 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 124 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 125 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 126 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 127 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 128 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 129 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 130 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 131 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 132 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 133 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 134 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 135 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 136 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 137 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 138 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 139 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 140 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 141 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 142 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 143 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 144 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 145 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 146 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 147 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 148 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 149 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 150 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 151 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 152 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 153 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 154 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 155 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 156 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 157 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 158 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 159 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 160 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 161 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 162 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 163 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 164 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 165 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 166 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 167 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 168 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 169 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 170 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 171 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 172 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 173 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 174 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 175 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 176 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 177 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 178 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 179 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 180 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 181 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 182 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 183 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 184 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 185 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 186 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 187 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 188 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 189 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 190 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 191 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 192 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 193 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 194 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 195 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 196 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 197 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 198 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 199 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 200 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 201 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 202 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 203 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 204 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 205 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 206 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 207 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 208 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 209 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 210 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 211 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 212 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 213 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 214 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 215 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 216 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 217 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 218 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 219 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 220 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 221 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 222 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 223 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 224 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 225 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 226 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 227 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 228 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 229 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 230 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 231 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 232 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 233 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 234 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 235 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 236 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 237 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 238 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 239 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 240 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 241 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 242 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 243 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 244 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 245 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 246 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 247 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 248 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 249 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 250 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 251 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 252 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 253 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 254 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 255 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 256 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 257 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 258 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 259 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 260 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 261 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 262 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 263 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 264 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 265 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 266 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 267 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 268 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 269 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 270 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 271 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 272 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 273 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 274 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 275 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 276 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 277 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 278 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 279 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 280 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 281 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 282 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 283 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 284 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 285 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 286 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 287 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 288 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 289 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 290 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 291 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 292 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 293 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 294 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 295 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 296 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 297 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 298 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 299 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 300 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 301 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 302 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 303 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 304 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 305 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 306 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 307 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 308 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 309 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 310 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 311 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 312 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 313 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 314 or a tautomer or pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (I) is Compound 315 or a tautomer or pharmaceutically acceptable salt thereof. The foregoing merely summarizes certain aspects of this disclosure and is not intended, nor should it be construed, as limiting the disclosure in any way. FORMULATION AND ROUTE OF ADMINISTRATION While it may be possible to administer a compound disclosed herein alone in the uses described, the compound administered normally will be present as an active ingredient in a pharmaceutical composition. Additionally, while the active ingredient in the pharmaceutical composition may be the compound, it can also be the tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer. Thus, in one embodiment, provided herein is a pharmaceutical composition comprising a compound disclosed herein in combination with one or more pharmaceutically acceptable excipients, such as diluents, carriers, adjuvants and the like, and, if desired, other active ingredients. See, e.g., Remington: The Science and Practice of Pharmacy, Volume I and Volume II, twenty-second edition, edited by Loyd V. Allen Jr., Philadelphia, PA, Pharmaceutical Press, 2012; Pharmaceutical Dosage Forms (Vol.1-3), Liberman et al., Eds., Marcel Dekker, New York, NY, 1992; Handbook of Pharmaceutical Excipients (3rd Ed.), edited by Arthur H. Kibbe, American Pharmaceutical Association, Washington, 2000; Pharmaceutical Formulation: The Science and Technology of Dosage Forms (Drug Discovery), first edition, edited by GD Tovey, Royal Society of Chemistry, 2018. In one embodiment, a pharmaceutical composition comprises a therapeutically effective amount of a compound disclosed herein. The compound(s) disclosed herein may be administered by any suitable route in the form of a pharmaceutical composition adapted to such a route and in a dose effective for the treatment intended. The compounds and compositions presented herein may, for example, be administered orally, mucosally, topically, transdermally, rectally, pulmonarily, parentally, intranasally, intravascularly, intravenously, intraarterial, intraperitoneally, intrathecally, subcutaneously, sublingually, intramuscularly, intrasternally, vaginally or by infusion techniques, in dosage unit formulations containing conventional pharmaceutically acceptable excipients. In some embodiments, the compounds and compositions presented herein may be orally, intravenously, or subcutaneously administered to the subject. In some embodiments, the compounds and compositions presented herein may be orally administered to the subject. The pharmaceutical composition may be in the form of, for example, a tablet, chewable tablet, minitablet, caplet, pill, bead, hard capsule, soft capsule, gelatin capsule, granule, powder, lozenge, patch, cream, gel, sachet, microneedle array, syrup, flavored syrup, juice, drop, injectable solution, emulsion, microemulsion, ointment, aerosol, aqueous suspension, or oily suspension. The pharmaceutical composition is typically made in the form of a dosage unit containing a particular amount of the active ingredient. According to some embodiments, the compound of the present disclosure may be administered at a dose in the range from about 0.5 mg to about 400 mg. In some embodiments, the compound is administered in a dose ranging from about 0.5 mg to about 380 mg, from about 0.5 mg to about 360 mg, from about 0.5 mg to about 340 mg, from about 0.5 mg to about 320 mg, from about 0.5 mg to about 300 mg, from about 0.5 mg to about 280 mg, from about 0.5 mg to about 260 mg, from about 0.5 mg to about 240 mg, from about 0.5 mg to about 220 mg, from about 0.5 mg to about 200 mg, from about 0.5 mg to about 180 mg, from about 0.5 mg to about 160 mg, from about 0.5 mg to about 140 mg, from about 0.5 mg to about 120 mg, from about 0.5 mg to about 100 mg, from about 0.5 mg to about 80 mg, from about 0.5 mg to about 60 mg, from about 0.5 mg to about 40 mg, from about 0.5 mg to about 20 mg, from about 0.5 mg to about 10 mg. In some embodiments, the compound of the present disclosure may be administered at a dose in the range from about 1 mg to about 400 mg. In some embodiments, the compound is administered in a dose ranging from about 1 mg to about 380 mg, from about 1 mg to about 360 mg, from about 1 mg to about 340 mg, from about 1 mg to about 320 mg, from about 1 mg to about 300 mg, from about 1 mg to about 280 mg, from about 1 mg to about 260 mg, from about 1 mg to about 240 mg, from about 1 mg to about 220 mg, from about 1 mg to about 200 mg, from about 1 mg to about 180 mg, from about 1 mg to about 160 mg, from about 1 mg to about 140 mg, from about 1 mg to about 120 mg, from about 1 mg to about 100 mg, from about 1 mg to about 80 mg, from about 1 mg to about 60 mg, from about 1 mg to about 40 mg, from about 1 mg to about 20 mg, from about 1 mg to about 10 mg. In some embodiments, the compound of the present disclosure may be administered at a dose in the range from about 2 mg to about 400 mg. In some embodiments, the compound is administered in a dose ranging from about 2 mg to about 380 mg, from about 2 mg to about 360 mg, from about 2 mg to about 340 mg, from about 2 mg to about 320 mg, from about 2 mg to about 300 mg, from about 2 mg to about 280 mg, from about 2 mg to about 260 mg, from about 2 mg to about 240 mg, from about 2 mg to about 220 mg, from about 2 mg to about 200 mg, from about 2 mg to about 180 mg, from about 2 mg to about 160 mg, from about 2 mg to about 140 mg, from about 2 mg to about 120 mg, from about 2 mg to about 100 mg, from about 2 mg to about 80 mg, from about 2 mg to about 60 mg, from about 2 mg to about 40 mg, from about 2 mg to about 20 mg, from about 2 mg to about 10 mg. In some embodiments, the compound is administered in a dose ranging from about 60 mg to about 400 mg, from about 60 mg to about 350 mg, from about 60 mg to about 320 mg, from about 30 mg to about 300 mg, from about 30 mg to about 250 mg, from about 30 mg to about 220 mg, from about 30 mg to about 200 mg, from about 30 mg to about 180 mg, from about 30 mg to about 160 mg, from about 20 mg to about 140 mg, from about 20 mg to about 120 mg, from about 15 mg to about 100 mg, from about 15 mg to about 80 mg, from about 6 mg to about 60 mg, from about 6 mg to about 40 mg, from about 6 mg to about 20 mg, from about 4 mg to about 10 mg. In some embodiments, the compound is administered at a dose of about 0.5 mg, about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, about 10 mg, about 11 mg, about 12 mg, about 13 mg, about 14 mg, about 15 mg, about 16 mg, about 17 mg, about 18 mg, about 19 mg, about 20 mg, about 21 mg, about 22 mg, about 23 mg, about 24 mg, about 25 mg, about 26 mg, about 27 mg, about 28 mg, about 29 mg, about 30 mg, about 31 mg, about 32 mg, about 33 mg, about 34 mg, about 35 mg, about 36 mg, about 37 mg, about 38 mg, about 39 mg, about 40 mg, about 41 mg, about 42 mg, about 43 mg, about 44 mg, about 45 mg, about 46 mg, about 47 mg, about 48 mg, about 49 mg, about 50 mg, about 51 mg, about 52 mg, about 53 mg, about 54 mg, about 55 mg, about 56 mg, about 56 mg, about 57 mg, about 58 mg, about 59 mg, about 60 mg, about 62 mg, about 64 mg, about 66 mg, about 68 mg, about 70 mg, about 72 mg, about 74 mg, about 76 mg, about 78 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, about 300 mg, about 325 mg, about 350 mg, about 375 mg, about 400 mg, or a range between any two of the preceding values. In some embodiments, the compound is administered at a dose of about 1 mg, about 2 mg, about 6 mg, about 18 mg, about 36 mg, about 72 mg, or about 140 mg. In some embodiments, the compound is administered at a dose of about about 6 mg, about 12 mg, about 25 mg, or about 50 mg. In some embodiments, the compound is administered at a dose of about 2 mg. In some embodiments, the compound is administered at a dose of about 6 mg. In some embodiments, the compound is administered at a dose of about 10 mg. In some embodiments, the compound is administered at a dose of about 12 mg. In some embodiments, the compound is administered at a dose of about 18 mg. In some embodiments, the compound is administered at a dose of about 25 mg. In some embodiments, the compound is administered at a dose of about 36 mg. In some embodiments, the compound is administered at a dose of about 50 mg. In some embodiments, the compound is administered at a dose of about 72 mg. In some embodiments, the compound is administered at a dose of about 140 mg. The dose can be achieved be administering a single pharmaceutically acceptable composition (e.g., a 400 mg dose can be achieved by administering a single a tablet comprising 400 mg of the compound or a 400 mg dose can be achieved by administering four tablets each comprising 100 mg of the compound). According to some embodiments, the compound is administered daily, weekly, bi- weekly, or monthly. In some embodiments, the compound is administered daily. In some embodiments, the compound is administered one or multiple times daily. In some embodiments, the compound is administered once per day. In some embodiments, the compound of the present disclosure may be administered at a daily dose in the range from about 0.5 mg to about 400 mg. In some embodiments, the compound is administered in a daily dose ranging from about 0.5 mg to about 380 mg, from about 0.5 mg to about 360 mg, from about 0.5 mg to about 340 mg, from about 0.5 mg to about 320 mg, from about 0.5 mg to about 300 mg, from about 0.5 mg to about 280 mg, from about 0.5 mg to about 260 mg, from about 0.5 mg to about 240 mg, from about 0.5 mg to about 220 mg, from about 0.5 mg to about 200 mg, from about 0.5 mg to about 180 mg, from about 0.5 mg to about 160 mg, from about 0.5 mg to about 140 mg, from about 0.5 mg to about 120 mg, from about 0.5 mg to about 100 mg, from about 0.5 mg to about 80 mg, from about 0.5 mg to about 60 mg, from about 0.5 mg to about 40 mg, from about 0.5 mg to about 20 mg, from about 0.5 mg to about 10 mg. In some embodiments, the compound of the present disclosure may be administered at a daily dose in the range from about 1 mg to about 400 mg. In some embodiments, the compound is administered in a daily dose ranging from about 1 mg to about 380 mg, from about 1 mg to about 360 mg, from about 1 mg to about 340 mg, from about 1 mg to about 320 mg, from about 1 mg to about 300 mg, from about 1 mg to about 280 mg, from about 1 mg to about 260 mg, from about 1 mg to about 240 mg, from about 1 mg to about 220 mg, from about 1 mg to about 200 mg, from about 1 mg to about 180 mg, from about 1 mg to about 160 mg, from about 1 mg to about 140 mg, from about 1 mg to about 120 mg, from about 1 mg to about 100 mg, from about 1 mg to about 80 mg, from about 1 mg to about 60 mg, from about 1 mg to about 40 mg, from about 1 mg to about 20 mg, from about 1 mg to about 10 mg. In some embodiments, the compound of the present disclosure may be administered at a daily dose in the range from about 2 mg to about 400 mg. In some embodiments, the compound is administered in a daily dose ranging from about 2 mg to about 380 mg, from about 2 mg to about 360 mg, from about 2 mg to about 340 mg, from about 2 mg to about 320 mg, from about 2 mg to about 300 mg, from about 2 mg to about 280 mg, from about 2 mg to about 260 mg, from about 2 mg to about 240 mg, from about 2 mg to about 220 mg, from about 2 mg to about 200 mg, from about 2 mg to about 180 mg, from about 2 mg to about 160 mg, from about 2 mg to about 140 mg, from about 2 mg to about 120 mg, from about 2 mg to about 100 mg, from about 2 mg to about 80 mg, from about 2 mg to about 60 mg, from about 2 mg to about 40 mg, from about 2 mg to about 20 mg, from about 2 mg to about 10 mg. In some embodiments, the compound is administered in a daily dose ranging from about 60 mg to about 400 mg, from about 60 mg to about 350 mg, from about 60 mg to about 320 mg, from about 30 mg to about 300 mg, from about 30 mg to about 250 mg, from about 30 mg to about 220 mg, from about 30 mg to about 200 mg, from about 30 mg to about 180 mg, from about 30 mg to about 160 mg, from about 20 mg to about 140 mg, from about 20 mg to about 120 mg, from about 15 mg to about 100 mg, from about 15 mg to about 80 mg, from about 6 mg to about 60 mg, from about 6 mg to about 40 mg, from about 6 mg to about 20 mg, from about 4 mg to about 10 mg. In some embodiments, the compound is administered at a daily dose of about 0.5 mg, about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, about 10 mg, about 11 mg, about 12 mg, about 13 mg, about 14 mg, about 15 mg, about 16 mg, about 17 mg, about 18 mg, about 19 mg, about 20 mg, about 21 mg, about 22 mg, about 23 mg, about 24 mg, about 25 mg, about 26 mg, about 27 mg, about 28 mg, about 29 mg, about 30 mg, about 31 mg, about 32 mg, about 33 mg, about 34 mg, about 35 mg, about 36 mg, about 37 mg, about 38 mg, about 39 mg, about 40 mg, about 41 mg, about 42 mg, about 43 mg, about 44 mg, about 45 mg, about 46 mg, about 47 mg, about 48 mg, about 49 mg, about 50 mg, about 51 mg, about 52 mg, about 53 mg, about 54 mg, about 55 mg, about 56 mg, about 56 mg, about 57 mg, about 58 mg, about 59 mg, about 60 mg, about 62 mg, about 64 mg, about 66 mg, about 68 mg, about 70 mg, about 72 mg, about 74 mg, about 76 mg, about 78 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, about 300 mg, about 325 mg, about 350 mg, about 375 mg, about 400 mg, or a range between any two of the preceding values. In some embodiments, the compound is administered at a daily dose of about 1 mg, about 2 mg, about 6 mg, about 18 mg, about 36 mg, about 72 mg, or about 140 mg. In some embodiments, the compound is administered at a daily dose of about about 6 mg, about 12 mg, about 25 mg, or about 50 mg. In some embodiments, the compound is administered at a daily dose of about 2 mg. In some embodiments, the compound is administered at a daily dose of about 6 mg. In some embodiments, the compound is administered at a daily dose of about 10 mg. In some embodiments, the compound is administered at a daily dose of about 12 mg. In some embodiments, the compound is administered at a daily dose of about 18 mg. In some embodiments, the compound is administered at a daily dose of about 25 mg. In some embodiments, the compound is administered at a daily dose of about 36 mg. In some embodiments, the compound is administered at a daily dose of about 50 mg. In some embodiments, the compound is administered at a daily dose of about 72 mg. In some embodiments, the compound is administered at a daily dose of about 140 mg. Pharmaceutically acceptable compositions According to some embodiments, the present disclosure provides a composition comprising a compound of this disclosure or a pharmaceutically acceptable derivative thereof and a pharmaceutically acceptable carrier, adjuvant, or vehicle. The amount of compound in compositions of this disclosure is such that it is effective to reduce soluble TREM2 levels in cerebrospinal fluid (“CSF”). In certain embodiments, the amount of compound in compositions of this disclosure is such that it is effective to measurably activate a TREM2 protein, or a mutant thereof, in a biological sample or in a patient. In certain embodiments, the amount of compound in compositions of this disclosure is such that it is effective to measurably activate a TREM2 protein, or a fragment thereof (i.e., soluble TREM2 (“sTREM2”), in a biological sample or in a patient. In certain embodiments, a composition of this disclosure is formulated for administration to a patient in need of such composition. In some embodiments, a composition of this disclosure is formulated for oral administration to a patient. Compositions of the present disclosure may be administered orally, parenterally, by inhalation spray, topically, rectally, nasally, buccally, vaginally or via an implanted reservoir. The term "parenteral" as used herein includes subcutaneous, intravenous, intramuscular, intra- articular, intra-synovial, intrasternal, intrathecal, intrahepatic, intralesional and intracranial injection or infusion techniques. Preferably, the compositions are administered orally, intraperitoneally or intravenously. Sterile injectable forms of the compositions of this disclosure may be aqueous or oleaginous suspension. These suspensions may be formulated according to techniques known in the art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non- toxic parenterally acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil may be employed including synthetic mono- or di- glycerides. Fatty acids, such as oleic acid and its glyceride derivatives are useful in the preparation of injectables, as are natural pharmaceutically-acceptable oils, such as olive oil or castor oil, especially in their polyoxyethylated versions. These oil solutions or suspensions may also contain a long-chain alcohol diluent or dispersant, such as carboxymethyl cellulose or similar dispersing agents that are commonly used in the formulation of pharmaceutically acceptable dosage forms including emulsions and suspensions. Other commonly used surfactants, such as Tweens, Spans and other emulsifying agents or bioavailability enhancers which are commonly used in the manufacture of pharmaceutically acceptable solid, liquid, or other dosage forms may also be used for the purposes of formulation. Pharmaceutically acceptable compositions of this disclosure may be orally administered in any orally acceptable dosage form including, but not limited to, capsules, tablets, aqueous suspensions or solutions. In the case of tablets for oral use, carriers commonly used include lactose and corn starch. Lubricating agents, such as magnesium stearate, are also typically added. For oral administration in a capsule form, useful diluents include lactose and dried cornstarch. When aqueous suspensions are required for oral use, the active ingredient is combined with emulsifying and suspending agents. If desired, certain sweetening, flavoring or coloring agents may also be added. Alternatively, pharmaceutically acceptable compositions of this disclosure may be administered in the form of suppositories for rectal administration. These can be prepared by mixing the agent with a suitable non-irritating excipient that is solid at room temperature but liquid at rectal temperature and therefore will melt in the rectum to release the drug. Such materials include cocoa butter, beeswax and polyethylene glycols. Pharmaceutically acceptable compositions of this disclosure may also be administered topically, especially when the target of treatment includes areas or organs readily accessible by topical application, including diseases of the eye, the skin, or the lower intestinal tract. Suitable topical formulations are readily prepared for each of these areas or organs. Topical application for the lower intestinal tract can be effected in a rectal suppository formulation (see above) or in a suitable enema formulation. Topically-transdermal patches may also be used. For topical applications, provided pharmaceutically acceptable compositions may be formulated in a suitable ointment containing the active component suspended or dissolved in one or more carriers. Carriers for topical administration of compounds of this disclosure include, but are not limited to, mineral oil, liquid petrolatum, white petrolatum, propylene glycol, polyoxyethylene, polyoxypropylene compound, emulsifying wax and water. Alternatively, provided pharmaceutically acceptable compositions can be formulated in a suitable lotion or cream containing the active components suspended or dissolved in one or more pharmaceutically acceptable carriers. Suitable carriers include, but are not limited to, mineral oil, sorbitan monostearate, polysorbate 60, cetyl esters wax, cetearyl alcohol, 2-octyldodecanol, benzyl alcohol and water. For ophthalmic use, provided pharmaceutically acceptable compositions may be formulated as micronized suspensions in isotonic, pH adjusted sterile saline, or, preferably, as solutions in isotonic, pH adjusted sterile saline, either with or without a preservative such as benzylalkonium chloride. Alternatively, for ophthalmic uses, the pharmaceutically acceptable compositions may be formulated in an ointment such as petrolatum. Pharmaceutically acceptable compositions of this disclosure may also be administered by nasal aerosol or inhalation. Such compositions are prepared according to techniques well-known in the art of pharmaceutical formulation and may be prepared as solutions in saline, employing benzyl alcohol or other suitable preservatives, absorption promoters to enhance bioavailability, fluorocarbons, and / or other conventional solubilizing or dispersing agents. Most preferably, pharmaceutically acceptable compositions of this disclosure are formulated for oral administration. Such formulations may be administered with or without food. In some embodiments, pharmaceutically acceptable compositions of this disclosure are administered without food. In other embodiments, pharmaceutically acceptable compositions of this disclosure are administered with food. The amount of compounds of the present disclosure that may be combined with the carrier materials to produce a composition in a single dosage form will vary depending upon the host treated, the particular mode of administration. Preferably, provided compositions should be formulated so that a dosage of between 0.01 - 200 mg / kg body weight / day of the compound can be administered to a patient receiving these compositions. In some embodiments, the compositions comprise about 0.5 mg to about 400 mg of the compound. In some aspects, the compositions comprise about 0.5 mg to about 375 mg, about 0.5 mg to about 350 mg, about 0.5 mg to about 325 mg, about 0.5 mg to about 300 mg, about 0.5 mg to about 275 mg, about 0.5 mg to about 250 mg, about 0.5 mg to about 225 mg, about 0.5 mg to about 200 mg, about 0.5 mg to about 175 mg, about 0.5 mg to about 150 mg, about 0.5 mg to about 125 mg, about 0.5 mg to about 100 mg, about 0.5 mg to about 75 mg, about 0.5 mg to about 50 mg, about 0.5 mg to about 25 mg, about 0.5 mg to about 10 mg, about 0.5 mg to about 5 mg, about 1 mg to about 400 mg, about 1 mg to about 375 mg, about 1 mg to about 350 mg, about 1 mg to about 325 mg, about 1 mg to about 300 mg, about 1 mg to about 275 mg, about 1 mg to about 250 mg, about 1 mg to about 225 mg, about 1 mg to about 200 mg, about 1 mg to about 175 mg, about 1 mg to about 150 mg, about 1 mg to about 125 mg, about 1 mg to about 100 mg, about 1 mg to about 75 mg, about 1 mg to about 50 mg, about 1 mg to about 25 mg, about 1 mg to about 10 mg, about 1 mg to about 5 mg, about 5 mg to about 400 mg, about 5 mg to about 375 mg, about 5 mg to about 350 mg, about 5 mg to about 325 mg, about 5 mg to about 300 mg, about 5 mg to about 275 mg, about 5 mg to about 250 mg, about 5 mg to about 225 mg, about 5 mg to about 200 mg, about 5 mg to about 175 mg, about 5 mg to about 150 mg, about 5 mg to about 125 mg, about 5 mg to about 100 mg, about 5 mg to about 75 mg, about 5 mg to about 50 mg, about 5 mg to about 25 mg, about 5 mg to about 10 mg, about 0.5 mg to about 5 mg, about 10 mg to about 400 mg, about 10 mg to about 375 mg, about 10 mg to about 350 mg, about 10 mg to about 325 mg, about 20 mg to about 300 mg, about 10 mg to about 275 mg, about 10 mg to about 250 mg, about 10 mg to about 225 mg, about 10 mg to about 200 mg, about 10 mg to about 175 mg, about 10 mg to about 150 mg, about 10 mg to about 125 mg, about 10 mg to about 100 mg, about 10 mg to about 75 mg, about 10 mg to about 50 mg, about 10 mg to about 25 mg, about 25 mg to about 400 mg, about 25 mg to about 375 mg, about 25 mg to about 350 mg, about 25 mg to about 325 mg, about 25 mg to about 300 mg, about 25 mg to about 275 mg, about 25 mg to about 250 mg, about 25 mg to about 225 mg, about 25 mg to about 200 mg, about 25 mg to about 175 mg, about 25 mg to about 150 mg, about 25 mg to about 125 mg, about 25 mg to about 100 mg, about 25 mg to about 75 mg, about 25 mg to about 50 mg, about 50 mg to about 400 mg, about 50 mg to about 375 mg, about 50 mg to about 350 mg, about 50 mg to about 325 mg, about 50 mg to about 300 mg, about 50 mg to about 275 mg, about 50 mg to about 250 mg, about 50 mg to about 225 mg, about 50 mg to about 200 mg, about 50 mg to about 175 mg, about 50 mg to about 150 mg, about 50 mg to about 125 mg, about 50 mg to about 100 mg, about 50 mg to about 75 mg, about 75 mg to about 400 mg, about 75 mg to about 375 mg, about 75 mg to about 350 mg, about 75 mg to about 325 mg, about 75 mg to about 300 mg, about 75 mg to about 275 mg, about 75 mg to about 250 mg, about 75 mg to about 225 mg, about 75 mg to about 200 mg, about 75 mg to about 175 mg, about 75 mg to about 150 mg, about 75 mg to about 125 mg, about 75 mg to about 100 mg, about 100 mg to about 400 mg, about 100 mg to about 375 mg, about 100 mg to about 350 mg, about 100 mg to about 325 mg, about 100 mg to about 300 mg, about 100 mg to about 275 mg, about 100 mg to about 250 mg, about 100 mg to about 225 mg, about 100 mg to about 200 mg, about 100 mg to about 175 mg, about 100 mg to about 150 mg, about 100 mg to about 125 mg, about 125 mg to about 400 mg, about 125 mg to about 375 mg, about 125 mg to about 350 mg, about 125 mg to about 325 mg, about 125 mg to about 300 mg, about 125 mg to about 275 mg, about 125 mg to about 250 mg, about 125 mg to about 225 mg, about 125 mg to about 200 mg, about 125 mg to about 175 mg, about 125 mg to about 150 mg, about 150 mg to about 400 mg, about 150 mg to about 375 mg, about 150 mg to about 350 mg, about 150 mg to about 325 mg, about 150 mg to about 300 mg, about 150 mg to about 275 mg, about 150 mg to about 250 mg, about 150 mg to about 225 mg, about 150 mg to about 200 mg, about 150 mg to about 175 mg, about 175 mg to about 400 mg, about 175 mg to about 375 mg, about 175 mg to about 350 mg, about 175 mg to about 325 mg, about 175 mg to about 300 mg, about 175 mg to about 275 mg, about 175 mg to about 250 mg, about 175 mg to about 225 mg, about 175 mg to about 200 mg, about 200 mg to about 400 mg, about 200 mg to about 375 mg, about 200 mg to about 350 mg, about 200 mg to about 325 mg, about 200 mg to about 300 mg, about 200 mg to about 275 mg, about 200 mg to about 250 mg, about 250 mg to about 400 mg, about 250 mg to about 375 mg, about 250 mg to about 350 mg, about 250 mg to about 325 mg, about 250 mg to about 300 mg, about 250 mg to about 275 mg, about 275 mg to about 400 mg, about 275 mg to about 375 mg, about 275 mg to about 350 mg, about 275 mg to about 325 mg, about 275 mg to about 300 mg, about 300 mg to about 400 mg, about 300 mg to about 375 mg, about 300 mg to about 350 mg, about 300 mg to about 325 mg, about 325 mg to about 400 mg, about 325 mg to about 375 mg, about 325 mg to about 350 mg, or about 375 mg to about 400 mg of the compound. In some embodiments, pharmaceutical composition comprises about 0.5 mg, about 1 mg, about 2.5 mg, about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, about 300 mg, about 325 mg, about 350 mg, about 375 mg, or about 400 mg of the compound. In some embodiments, the pharmaceutical composition comprises about 1, about 5, about 25, or about 100 mg of the compound. In some embodiments, the pharmaceutical composition comprises about 1 mg, about 2 mg, about 6 mg, about 18 mg, about 36 mg, about 72 mg, or about 140 mg of the compound. In some embodiments, the pharmaceutical composition comprises about about 6 mg, about 12 mg, about 25 mg, or about 50 mg of the compound. In some embodiments, the pharmaceutical composition comprises about 2 mg of the compound. In some embodiments, the pharmaceutical composition comprises about 6 mg of the compound. In some embodiments, the pharmaceutical composition comprises about 10 mg of the compound. In some embodiments, the pharmaceutical composition comprises about 12 mg. In some embodiments, the pharmaceutical composition comprises about 18 mg of the compound. In some embodiments, the pharmaceutical composition comprises about 25 mg of the compound. In some embodiments, the pharmaceutical composition comprises about 36 mg of the compound. In some embodiments, the pharmaceutical composition comprises about 50 mg of the compound. In some embodiments, the pharmaceutical composition comprises about 72 mg of the compound. In some embodiments, the pharmaceutical composition comprises about 140 mg of the compound. In certain embodiments, pharmaceutical compositions provided herein are formulated to comprise a fixed amount of an active ingredient selected from about 0.5 mg, about 0.75 mg, about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, about 10 mg, about 11 mg, about 12 mg, about 13 mg, about 14 mg, about 15 mg, about 16 mg, about 17 mg, about 18 mg, about 19 mg, about 20 mg, about 21 mg, about 22 mg, about 23 mg, about 24 mg, about 25 mg, about 26 mg, about 27 mg, about 28 mg, about 29 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, about 100 mg, about 105 mg, about 110 mg, about 115 mg, about 120 mg, about 125 mg, about 130 mg, about 135 mg, about 140 mg, about 145 mg, about 150 mg, about 155 mg, about 160 mg, about 170 mg, about 175 mg, about 180 mg, about 185 mg, about 190 mg, about 195 mg, about 200 mg, about 205 mg, about 210 mg, about 215 mg, about 220 mg, about 225 mg, about 230 mg, about 235 mg, about 240 mg, about 245 mg, about 250 mg, about 255 mg, about 260 mg, about 265 mg, about 270 mg, about 275 mg, about 280 mg, about 285 mg, about 290 mg, about 295 mg, about 300 mg, about 305 mg, about 310 mg, about 315 mg, about 320 mg, about 325 mg, about 330 mg, about 335 mg, about 340 mg, about 345 mg, about 350 mg, about 355 mg, about 360 mg, about 365 mg, about 370 mg, about 375 mg, about 380 mg, about 385 mg, about 390 mg, about 395 mg, or about 400 mg such active ingredient being a compound disclosed herein or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer. It should also be understood that a specific dosage and treatment regimen for any particular patient will depend upon a variety of factors, including the activity of the specific compound employed, the age, body weight, general health, sex, diet, time of administration, rate of excretion, drug combination, and the judgment of the treating physician and the severity of the particular disease being treated. The amount of a compound of the present disclosure in the composition will also depend upon the particular compound in the composition. ENUMERATED EMBODIMENTS 1. A method of treating Alzheimer’s Disease in a subject in need thereof, the method comprising administering to the subject a dosage of about 0.5 mg to about 400 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 2. The method of embodiment 1, wherein the dosage is about 1 mg to about 400 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 3. The method of any one of the preceding embodiments, wherein the dosage is about 2 mg to about 400 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 4. The method of any one of the preceding embodiments, wherein the dosage is about 0.5 mg to about 140 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 5. The method of any one of the preceding embodiments, wherein the dosage is about 0.5 mg to about 100 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 6. The method of any one of the preceding embodiments, wherein the dosage is about 0.5 mg to about 80 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 7. The method of any one of the preceding embodiments, wherein the dosage is about 0.5 mg to about 60 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 8. The method of any one of the preceding embodiments, wherein the dosage is about 0.5 mg to about 40 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 9. The method of any one of the preceding embodiments, wherein the dosage is about 0.5 mg to about 20 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 10. The method of any one of the preceding embodiments, wherein the dosage is about 0.5 mg to about 10 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 11. The method of any one of the preceding embodiments, wherein the dosage is about 1 mg, about 2 mg, about 6 mg, about 18 mg, about 36 mg, about 72 mg, or about 140 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 12. The method of any one of the preceding embodiments, wherein the dosage is about 6 mg, about 12 mg, about 25 mg, or about 50 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 13. The method of any one of the preceding embodiments, wherein the small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof is orally, intravenously, or subcutaneously administered to the subject. 14. The method of any one of the preceding embodiments, wherein the small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof is orally administered to the subject. 15. The method of any one of the preceding embodiments, wherein the small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof is orally administered to the subject as a tablet, chewable tablet, minitablet, caplet, pill, bead, hard capsule, soft capsule, gelatin capsule, granule, powder, lozenge, patch, syrup, flavored syrup, or juice. 16. The method of any one of the preceding embodiments, wherein the small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof is orally administered to the subject as a tablet, hard capsule, soft capsule, or gelatin capsule. 17. The method of any one of the preceding embodiments, wherein the small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof is administered daily, weekly, biweekly, or monthly. 18. The method of any one of the preceding embodiments, wherein the small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof is administered daily. 19. The method of any one of the preceding embodiments, wherein the small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof is administered once or multiple times daily. 20. The method of any one of the preceding embodiments, wherein the small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof is administered once or twice daily. 21. The method of any one of the preceding embodiments, wherein the small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof is administered once daily. 22. The method of any one of the preceding embodiments, wherein the subject has a mutation in TREM2. 23. The method of any one of the preceding embodiments, wherein the subject has one or more of R47H, R62H, H157Y, D87N, T96K, or L211P variants of TREM2. 24. The method of any one of the preceding embodiments, wherein the subject has one or more microglia-associated Alzheimer’s Disease risk gene variants. 25. The method of embodiment 24, wherein the one or more microglia-associated Alzheimer’s Disease risk gene variants is APOE4, MS4A, CD33, CLU, INPPSD, or CR1. 26. The method of any one of the preceding embodiments, wherein the subject has been identified and / or diagnosed as having Alzheimer’s Disease. 27. The method of any one of the preceding embodiments, wherein the subject has a diagnosis of mild cognitive impairment due to Alzheimer’s Disease. 28. The method of any one of the preceding embodiments, wherein the subject has a diagnosis of mild Alzheimer’s Disease according to the 2018 National Institutes on Aging and Alzheimer’s Association criteria. 29. The method of any one of the preceding embodiments, wherein the subject has a MMSE score of 18 to 30 (inclusive). 30. The method of any one of the preceding embodiments, wherein the subject is asymptomatic for Alzheimer’s Disease. 31. The method of any one of the preceding, wherein the small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof is administered to the subject prior to the onset of signs or symptoms of Alzheimer’s Disease. 32. The method of any one of the preceding embodiments, wherein the subject is aged 18 years or older. 33. The method of any one of the preceding embodiments, wherein the small molecule TREM2 agonist is a compound of Formula (I): or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein Ring A together with the 6-membered ring system to which it is fused forms a bicyclic ring system selected from:

[0006] wherein X1is CR10or N; X2is C(R10)2, O, C(=O), S(O)2, or NR10; X3is CR10or N; X4is CR10or N; X5is CR10or N; X6is CR10, N, or NR10; X7is CR10or N; X8is CR10or N; X9is CR10or N; X10is CR10, C(R10)2, O, S or NR10; X11is C or N; X12is CR10or NR10; X13is C or N; X23is CR10, N, NR10, SO2, or C=O; X24is CR10, N, NR10, SO2, or C=O; X25is CR10, N, NR10, SO2, or C=O; L is a bond or an optionally substituted straight chain or branched C1-6 alkylene; wherein the straight chain or branched C1-6 alkylene is optionally substituted with C1-6 alkyl, hydroxyl, or -N(RB)(RC); R1aand R1bis each independently H, C1-6alkyl or C1-6heteroalkyl; R2aand R2bis each independently H, D, C1-6 alkyl, C1-6 haloalkyl, C1-6 heteroalkyl, C3- 8cycloalkyl, or C3-8 heterocyclic; R3is H, D, C1-6 alkyl, or C1-6 heteroalkyl; or R1a, R1b, and R3are taken together with their intervening atoms to form a cyclic group selected from a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring; R4is C1-6 alkyl, C2-6 alkenyl, C1-6 haloalkyl, C1-6 heteroalkyl, C3-8 cycloalkyl, C3-8 heterocycloalkyl, aryl, heteroaryl, -O(RA), -N(RB)(RC), C(=O)(C1-6alkyl), -C(=O)O(C1-6alkyl), - C(=O)(cycloalkyl), -C(=O)(heterocyclic), or -C(=O)(heteroaryl), wherein alkyl, alkenyl, haloalkyl, heteroalkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl are optionally further substituted with 1-6 R11; R5is C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C1-6 heteroalkyl, C3-8 cycloalkyl, C3-8 heterocyclic, aryl, heteroaryl, halogen, cyano, -O(RA), -N(RB)(RC), C(=O)(C1-6alkyl), - C(=O)O(C1-6alkyl), -C(=O)(cycloalkyl), -C(=O)(heterocyclic), or -C(=O)(heteroaryl), wherein alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl are optionally further substituted with 1-6 R11; R6and R7are each independently H, D, C1-6 alkyl, C2-6 alkenyl, C1-6 heteroalkyl, C1-6 haloalkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, halogen, cyano, -O(RA), or -N(RB)(RC), wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclic, aryl, and heteroaryl is optionally substituted with one or more R12; or wherein the R6and R7groups together with the carbons to which they are attached form a 5- membered heterocyclic group; R8aand R8bare each independently H or C1-6alkyl; or R8aand R8bare taken together with their intervening atoms to an oxo group; R9is H or C1-6 alkyl; R10is H, C1-6 alkyl, C1-6 heteroalkyl, C1-6 haloalkyl, heteroaryl, halogen, cyano, - O(RA), -N(RB)(RC), or -N(RB), wherein heteroaryl is optionally further substituted with 1-6 R11, or wherein any two R10groups together with the carbons to which they are attached at X23, X24, or X25form a 5-membered heterocyclic group; R11and R12are each independently H, D, C1-6 alkyl, C1-6 heteroalkyl, C1-6 haloalkyl, halogen, oxo, -O(RA), or -N(RB)(RC); each RAis independently H, D, C1-6alkyl, C1-6heteroalkyl, C1-6haloalkyl, cycloalkyl, heterocyclic, or -N(RB)(RC); each RBand RCis independently H, C1-6 alkyl, C1-6 heteroalkyl, C1-6 heteroaralkyl, C1-6 haloalkyl, cycloalkyl, heterocyclic, or -C(O)-alkyl, wherein the C1-6 alkyl or heterocyclic is optionally further substituted with cycloalkyl or –O(RA); R13is an optionally substituted C1-6 aliphatic group, halogen, -OR, -CN, -NR2, -C(=O)R, -C(=O)OR, -C(=O)NR2, -SO2R, -SO2NR2, C1-6haloalkyl, or C1-6haloalkoxy; n is 0, 1, or 2; and m is 0, 1, or 2. 34. The method of any one of the preceding embodiments, wherein the small molecule TREM2 agonist is a compound of Formula (II): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in embodiment 33. 35. The method of any one of embodiments 1-33, wherein the small molecule TREM2 agonist is a compound of Formula (II): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein X1is CR10or N; X2is C(R10)2 or O; R2aand R2bis each independently H, D, methyl, , , ; R3is H or D; , , , r

[0007] ; R6is H, methyl, propyl, R7is methyl, 36. The method of any one of embodiments 1-33, wherein the small molecule TREM2 agonist is a compound of Formula (III): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in embodiment 33. 37. The method of any one of embodiments 1-33, wherein the small molecule TREM2 agonist is a compound of Formula (IV): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in embodiment 33. 38. The method of any one of embodiments 1-33, wherein the small molecule TREM2 agonist is a compound of Formula (V): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in embodiment 33. 39. The method of any one of embodiments 1-33, wherein the small molecule TREM2 agonist is a compound of Formula (VI): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in embodiment 33. 40. The method of any one of embodiments 1-33, wherein the small molecule TREM2 agonist is a compound of Formula (VII): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in embodiment 33. 41. The method of any one of embodiments 1-33, wherein the small molecule TREM2 agonist is a compound of Formula (VIII): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in embodiment 33. 42. The method of any one of embodiments 1-33, wherein the small molecule TREM2 agonist is a compound of Formula (IX): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in embodiment 33. 43. The method of any one of embodiments 1-33, wherein the small molecule TREM2 agonist is a compound of Formula (X): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in embodiment 33. 44. The method of any one of embodiments 1-33, wherein the small molecule TREM2 agonist is a compound of Formula (XI): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in embodiment 33. 45. The method of any one of embodiments 1-33, wherein the small molecule TREM2 agonist is a compound of Formula (XII): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in embodiments 33. 46. The method of any one of embodiments 1-33, wherein the small molecule TREM2 agonist is a compound of Formula (XIII): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in embodiment 33. 47. The method of any one of embodiments 1-33, wherein the small molecule TREM2 agonist is a compound of Formula (XIV): tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in embodiment 33. 48. The method of any one of the preceding embodiments, wherein the small molecule TREM2 agonist is a compound selected from Table A, or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer. 49. The method of any one of the preceding embodiments, wherein the dosage is about 2 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 50. The method of any one of embodiments 1-48, wherein the dosage is about 6 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 51. The method of any one of embodiments 1-48, wherein the dosage is about 10 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 52. The method of any one of embodiments 1-48, wherein the dosage is about 12 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 53. The method of any one of embodiments 1-48, wherein the dosage is about 18 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 54. The method of any one of embodiments 1-48, wherein the dosage is about 25 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 55. The method of any one of embodiments 1-48, wherein the dosage is about 36 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 56. The method of any one of embodiments 1-48, wherein the dosage is about 50 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 57. The method of any one of embodiments 1-48, wherein the dosage is about 72 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 58. The method of any one of embodiments 1-48, wherein the dosage is about 140 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof. 59. The method of any one of embodiments 1-48, wherein after being administered the compound of Formula (I) disclosed herein once daily for 14 days, the subject exhibits at least a 10% decrease in the concentrations of soluble TREM2 (sTREM2) in the CSF after administration as compared with the levels prior to administration of the compound. 60. The method of any one of embodiments 1-48, wherein after being administered the compound of Formula (I) disclosed herein once daily for 14 days, the subject exhibits a 70%, a 65%, a 60%, a 55%, a 50%, a 45%, a 40%, a 35%, a 30%, a 25%, a 20%, a 15%, or a 10% decrease in the concentrations of sTREM2 in the CSF as compared with the levels prior to administration of the compound. EXAMPLES Compounds described herein can be prepared by methods known to one of ordinary skill in the art, for example, as described in WO / 2021 / 226629, WO2022 / 236,272, WO2023 / 086799, WO2023 / 086800, and WO2023 / 086801, the contents of which are incorporated herein by reference in their entireties. LIST OF ABBREVIATIONS

[0008] Example 1. Phase 1, First-in-human, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study in Healthy Adults and Open-label Single Dose Study in Patients with Alzheimer’s Disease to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Rationale Microglia and neuroinflammation are strongly implicated in the genetics and neuropathology of Alzheimer’s disease (AD). The role of microglial dysfunction in plaque development in AD is based on the observation that normally functioning microglia reduce levels of toxic amyloid plaques in the brain, while increasing the number of inert, dense core plaques. In addition, dysfunction in triggering receptor expressed on myeloid cells 2 (TREM2) function is reported to exacerbate AD-associated tau accumulation and spreading. Loss-of-function TREM2 variants occur in 7% to 8% of the AD population and are linked both to disease progression and to worsened patient outcomes. For example, the R47H TREM2 variant, which represents 2% to 3% of the AD population, has been reported to triple the risk of AD in genome-wide association studies and to be associated with a 23% faster rate of dementia as compared with nonvariant carriers. This first-in-human, Phase 1 study will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of a compound of Formula (I) disclosed herein in healthy adult participants after administration of single and multiple oral doses of the compound and in patients with Alzheimer’s disease after administration of single oral dose of the compound. Objectives and Endpoints The study objectives and endpoints are summarized in Table 1. Table 1: Study Objectives and Endpoints

[0009] Overall Design SAD Portion (Part A) This is a randomized, double-blind (sponsor-open), placebo-controlled, single-dose study of the safety, tolerability, PK, and PD of the compound when administered orally to healthy adult participants over 18 years of age. The study will include a Screening / Baseline Period (up to 28 days), a Treatment Period (1 day), and a Safety Follow-up Period (35 days after dosing on Day 1). Eight participants will be randomized into each of up to 7 planned cohorts with additional cohorts optional. In each cohort, participants will be randomized in a 6:2 allocation ratio to compound or placebo. The dose will be sequentially escalated in each subsequent cohort until the maximum tolerated single dose or a dose that is expected to achieve mean exposures at or below the exposure limit s reached. Depending on the safety and tolerability assessments and interim PK data, the planned doses may be adjusted, repeated, or not conducted. Sentinel dosing is planned for all SAD dose-escalation cohorts. The first 2 participants in each cohort will be randomized and administered investigational medicinal product (IMP) such that 1 participant will receive the compound and 1 participant will receive placebo. The remaining 6 healthy adult participants will be randomized in a 5:1 allocation ratio to compound or placebo and dosing will be in a staggered fashion, such that no two subjects after the sentinel pair are dosed simultaneously. These 6 participants will not be administered IMP until the investigator has reviewed safety data up to 72 hours after dosing for the first 2 participants (sentinel participants) in the cohort. The planned cohorts and randomization scheme (SAD portion) are shown in Table 2 below. Table 2. Planned Cohorts and Randomization Scheme (SAD Portion)

[0010] The SAD cohorts will be tested sequentially in a dose-escalating manner. Pharmacokinetic data through 24 hours and at least 4 days of safety data will be reviewed by a Safety Review Committee (SRC) before dose escalation. Safety data from a minimum of 6 participants through at least 4 days after dosing must be available to trigger the safety review. Participants who discontinue from the study may be replaced at the discretion of the sponsor. Participants will be admitted to the Clinical Research Unit (CRU) on Day -2 and will remain confined to the CRU until all assessments have been completed on Day 8 (9 nights). Serial PK blood sampling, cerebrospinal fluid (CSF) collection via lumbar puncture, and safety assessments will be conducted (as shown in the Schedule of Assessments in Table 2) before and after administration of IMP. Cerebrospinal fluid collection may be performed in all or in a subset of cohorts at the discretion of the sponsor.

[0011] MAD Portion (Part B) This is a randomized, double-blind (sponsor-open), placebo-controlled study of the safety, tolerability, PK, and PD of the compound when administered orally, once daily, to healthy vasectomized males or women not of childbearing potential aged 18 to 64 years for 14 days. The study will include a Screening / Baseline Period (up to 28 days), a Treatment Period (14 days), and a Safety Follow-up Period (28 days after the last dose on Day 14). Eight participants will be randomized into each of up to 4 planned cohorts (Cohorts 1B- 4B). In each cohort, participants will be randomized in a 6:2 allocation ratio to compound or placebo and will receive their randomized treatment once daily for 14 days. Subjects in the MAD cohorts will be dosed in a staggered fashion on Day 1, such that no two subjects are dosed simultaneously. Doses for the MAD portion of the study will be determined as the study progresses and may be adjusted based on ongoing assessments. The dose of the compound will be escalated in each successive cohort until the maximum tolerated dose is reached or the maximum planned once-daily multiple dose (i.e., Cohort 4B) is reached. Depending on the safety and tolerability assessments and interim PK data, the planned doses may be adjusted, repeated, or not conducted. The planned doses and randomization scheme for the MAD portion is provided in Table 3. Table 3. Planned Doses and Randomization Scheme (MAD Portion) Sentinel dosing will not be used during the MAD portion of the study. All doses that are administered in the MAD cohorts will have been previously shown to be safe and well tolerated in healthy adult participants when administered as a single dose in the SAD portion of the study, and the projected mean exposure (based on maximum plasma drug concentration [Cmax] or area under the concentration-time curve from time zero to the dosing interval (i.e.24 hours) [AUC0-tau]) will not exceed the mean exposures that have been observed at the doses in the SAD portion of the study. The MAD cohorts will be conducted sequentially in a dose-escalating manner. Pharmacokinetic data through Day 14 and at least 4 days of safety data after the last dose of IMP will be reviewed by the SRC before dose escalation. Safety data from a minimum of 6 participants through at least 4 days after the last dose on Day 14 must be available to trigger the safety review for dose escalation. Participants who discontinue from the study may be replaced at the discretion of the sponsor. Participants will be admitted to the CRU on Day -2 and will remain confined to the CRU until all assessments have been completed on Day 21 (22 nights). Serial PK blood sampling, CSF collection via lumbar puncture, and safety assessments will be conducted before and after administration of IMP. Cerebrospinal fluid collection may be performed in all or in a subset of cohorts at the discretion of the sponsor. Participants will be contacted by telephone on approximately Day 42 (approximately 28 days after the last dose of IMP) to inquire about the occurrence of any adverse events since discharge from the CRU.

[0012] Alzheimer’s Disease Portion (Part C) This is an open-label, single-dose, biomarker study of the compound in participants aged 50 years and older with a diagnosis of mild cognitive impairment (MCI) due to AD or mild AD according to the 2018 National Institute on Aging and Alzheimer’s Association (NIA-AA) criteria which requires biomarker evidence of amyloid pathology (Stages 3 and 4 per FDA draft guidance for industry on Early Alzheimer’s Disease: Developing Drugs for Treatment, March 2024). Participants must have a MMSE score of 18 to 30 (inclusive). Approximately 10 patients with Alzheimer’s disease may be enrolled. The objective of Part C is to evaluate safety, tolerability, PK and to explore whether effects on PD biomarkers after single-dose of the compound are similar to healthy volunteers to inform dose selection for subsequent development in Alzheimer’s disease. Part C of the study will commence after satisfactory review of relevant data from Part A. This approach will provide compound safety, PK and PD data to inform dose selection for Part C in AD patients. The dose administered in the AD cohort will have been previously shown to be safe, well tolerated and shown to have an effect on biomarkers in healthy adult participants when administered as a single dose in the SAD portion of the study. Participants in the AD cohort will be dosed in a staggered fashion on Day 1, such that no two participants are dosed simultaneously. The study will include a Screening Period (8 weeks), Treatment Period (1 day), and a Safety Follow-up Period (Day 29). The total duration of study participation for each participant will be approximately 12 weeks. After providing written informed consent, participants will undergo screening evaluations, which will include collection of a blood sample for analysis of amyloid-beta (Aβ) peptide and genetic screening. Participants will be genotyped to determine if they are a TREM2 variant carrier (e.g. R47H, R62H, H157Y, D87N, T96K, L211P), an APOE4 carrier, or an APOE4 noncarrier. Participants who satisfy all protocol eligibility criteria will receive a single dose of the compound on Day 1. Participants will be admitted to the Clinical Research Unit (CRU) on Day -2 and will remain confined to the CRU until all assessments have been completed on Day 2 (3 nights). Serial PK blood sampling, CSF collection via lumbar puncture, and safety assessments will be conducted before and after administration of IMP. Participants will complete a follow-up safety phone call on Day 29, 28 days after dosing. Dose escalation may be halted for any of the following reasons: . Two or more participants develop the same category of Grade ≥2 (moderate) adverse event that is considered related to the IMP or for which there is no alternative, plausible, or attributable cause. . Grade ≥3 (severe) adverse events that are considered related to the IMP or for which there is no alternative, plausible, or attributable cause occur in 1 or more of the participants in a cohort. . One participant develops a serious adverse event that is considered related to the IMP or for which there is no alternative, plausible, or attributable cause. . The limit of safety and / or tolerability has been reached. The investigator will use reasonable clinical judgment to determine the severity of adverse events based on the US Food and Drug Administration (FDA) Toxicity Grading Scale. The study may be stopped if any of the following occurs: . Two or more participants develop the same category of Grade 3 (severe) adverse event that is considered related to the IMP or for which there is no alternative, plausible, or attributable cause. . One participant develops a Grade 4 (potentially life threatening) or serious adverse event that is considered related to the IMP or for which there is no alternative, plausible, or attributable cause. . A participant dies at any time, and the death is considered related to the IMP or there is no alternative, plausible, or attributable cause. The investigator will use reasonable clinical judgment to determine the severity of adverse events based on the US FDA Toxicity Grading Scale. Inclusion Criteria for SAD and MAD Participants may be eligible for the study if any of the following apply: . SAD: The participant is an adult over 18 years of age at the Screening Visit. . MAD: The participant is an adult over the age of 18 years at the Screening Visit. . The participant is deemed healthy by the principal investigator, as determined by prestudy medical evaluation (medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory evaluations). . The participant has a body mass index (BMI) between 18.5 and 32.0 kg / m2, inclusive, at the Screening Visit. . The participant has a negative urine cotinine test at the Screening Visit and at admission to the CRU. Exclusion Criteria for SAD and MAD Participants may be excluded from the study if any of the following apply: Medical Conditions . The participant is a female of childbearing potential. . The participant has a clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological, psychiatric disorder(s), or hematological or coagulation disorders as determined by the principal investigator. . The participant has any concurrent disease or condition that, in the opinion of the principal investigator, would make the participant unsuitable for participation in the clinical study. . The participant has clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at the Screening Visit and at admission to the CRU. Abnormalities that the principal investigator considers not clinically significant are acceptable. . The participant has clinically significant abnormal findings on physical examination (at admission to the CRU) or 12-lead ECG (at the Screening Visit or at admission to the CRU) based on the discretion of the investigator or designee. . The participant has a clinically significant alcohol or substance use disorder (other than caffeine or nicotine), as defined by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (American Psychiatric Association, 2013), within 1 year before the Screening Visit. . The participant has had any malignancy in the 5 years prior to screening, excluding basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ that has been successfully treated. . The participant is an active smoker or tobacco user (e.g., chew, snuff) and is unable to discontinue tobacco use at least 4 weeks before admission to the CRU and refrain from using tobacco during the study. . The participant has a history of hypersensitivity to the IMP, to any of the excipients, or to medicinal products with similar chemical structures. . The participant has donated blood (>500 mL) or blood products within 2 months (56 days) before admission to the CRU. . The participant has had a severe course of COVID-19, defined as extracorporeal membrane oxygenation, mechanically ventilated, and / or stay in an intensive care unit. Prior / Concomitant Medications . The participant has been administered an investigational drug within 30 days or 5 half-lives, whichever is longer, before admission to the CRU. . The participant has received a final dose of COVID-19 vaccine within 14 days before admission to the CRU (i.e., participant must have completed vaccination at least 14 days before admission to the CRU). . The participant has used prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication. Herbal supplements and hormone replacement therapy must be discontinued at least 28 days prior to the first dose of study medication. As an exception, acetaminophen / paracetamol may be used at doses of ≤1 g / day. Limited use of non-prescription medications that are not believed to affect subject safety or the overall results of the study may be permitted on a case-by-case basis following approval by the sponsor. . The participant has used any chronic medications within 30 days before the baseline visit or will require use of such medications throughout the stay at the CRU. Screening / Admission to CRU Tests . The participant has vital signs that are out of range at the Screening Visit or at admission to the CRU. In this case, the principal investigator may obtain 2 additional measurements of vital signs. If vital signs are out of range in ≥3 assessments and are considered to be clinically relevant in the judgement of the principal investigator, the participant is not eligible for the study. . The participant has a positive test for hepatitis B surface antigen (HbsAg), hepatitis C antibody, or human immunodeficiency virus (HIV) antibody. . The participant has positive breath or urine test for ethanol at the Screening Visit or at admission to the CRU. . The participant has a positive urine drug screen (e.g., cocaine, amphetamines, barbiturates, opiates, benzodiazepines, cannabinoids) or cotinine test at the Screening Visit or at admission to the CRU. . The participant has clinical signs and symptoms consistent with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection (e.g., fever, dry cough, dyspnea, sore throat, fatigue, laboratory-confirmed acute infection with SARS-CoV-2) at admission to the CRU. Other Exclusion Criteria . The participant is unable to understand the protocol requirements, instructions, study related restrictions, or the nature, scope, and possible consequences of the clinical study. . The participant is unlikely to comply with the protocol requirements, instructions, or study-related restrictions (e.g., uncooperative attitude, inability to return for follow-up visits, improbability of completing the clinical study). . The participant has previously been randomized in this clinical study. . The participant does not meet the CRU policies for COVID-19 testing or history. Additional Exclusion Criteria for Participants in CSF Cohorts A participant who meets one or more of the following criteria may not be considered for inclusion in the SAD / MAD cohorts that include CSF assessments: . The participant has hypersensitivity to the anesthetic that will be used during CSF collection or to any medication that is used to prepare the area of the lumbar puncture. . The participant has undergone previous CSF collection unrelated to this study within 30 days before admission to the CRU. . The participant has a history of vertebral deformities, major lumbar back surgery, clinically significant back pain, clinically significant abnormal x-ray findings, and / or injury that, in the opinion of the principal investigator, would preclude the participant from participating in CSF collection during the study. . The participant has an ongoing skin infection at the lumbar puncture injection site or scar tissue on the back that would interfere with a lumbar puncture. . The participant has clinically significant values outside of the normal reference range for coagulation tests (prothrombin time / international normalized ratio, partial thromboplastin time) or a platelet count below the normal reference range at the Screening Visit. Inclusion Criteria AD Participants may be eligible for the study if any of the following apply: General and Administrative . The participant is older than 18 years of age on the day the informed consent form (ICF) is signed. . In the investigator’s judgement, is able to understand the nature of the study, comply with protocol requirements including scheduled visits, blood and CSF sampling, and other study procedures, and is capable of providing written informed consent to participate in the study, or has a study partner or legal guardian who can understand and assist the participant in complying with the protocol requirements and provide written informed consent with participant assent. . Must consent to genotyping for apolipoprotein E (APOE), Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) and other dementia risk genes. . The participant has a body mass index (BMI) between 18.5 and 32.0 kg / m2, inclusive, at the Screening Visit. . Received the approval of Sponsor medical personnel as to final eligibility for the study. Type of Participant and Disease Characteristics . Satisfies the criteria for MCI due to AD or mild AD according to 2018 NIA-AA criteria. Note: Participants with a TREM2 variant (e.g. R47H, R62H) who have subjective memory or cognitive complaints and meet all other eligibility criteria may be enrolled with Sponsor approval. . Score of 18 to 30, inclusive, on the Mini-Mental State Examination (MMSE) (Folstein MF, et al. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res., 12(3):189–98 (1975). . Evidence of cerebral amyloid pathology based on blood test (test at central lab). Historical PET scan (conducted within 12 months prior to Screening) may be permissible for eligibility with Sponsor approval. The scan and local radiological report must be submitted. . The participant should be in good health as determined by the Investigator, based on medical history and screening assessments. Exclusion Criteria for AD Participants are excluded from the study if any of the following apply: Prior / Concomitant Therapy . Use of medications that are moderate or strong CYP3A4 inhibitors and / or inducers. . Received passive immunotherapy (within 6 months of Screening), anti-amyloid treatment (within 6 months of Screening) or active immunotherapy or gene therapy. . Use of allowed chronic medications at doses that have not been stable for at least 4 weeks prior to Screening Visit or use of AD medications (including but not limited to donepezil, rivastigmine, galantamine, tacrine, and memantine) at doses that have not been stable for at least 8 weeks prior to Screening Visit. . Vaccinations within 14 days prior to Baseline (Day -2) . Currently enrolled in another investigational drug or device study or has received an investigational product within 30 days or 5 half-lives (which-ever is longer) before signing the ICF for this study. Other Exclusion Criteria . Any condition or situation that, in the opinion of the investigator or sponsor medical personnel, may place the participant at significant risk, confound the study results, or interfere significantly with the participant's participation in the study. Lifestyle Considerations Participants in the SAD are advised to fast overnight (at least 10 hours) and remain fasting for at least 4 hours after dosing. Participants in the AD part are advised to fast overnight (at least 8 hours) and remain fasting for at least 4 hours after dosing. Participants in the MAD must fast overnight (at least 10 hours) and remain fasting for at least 4 hours after dosing on serial PK sampling days (Days 1, 7 and 14). On all other days (Days 2-6 and 8-13) investigational product is to be administered outside a window of + / -2 hours of giving food. Participants may consume water as desired except for 1 hour before and 1 hour after administration of IMP. If fed (if applicable for SAD, AD cohorts), the following guidelines apply for dosing while investigating food effect or dose escalation under fed conditions in the study: . Following an overnight fast of at least 10 hours (SAD) or 8 hours (AD), subjects should start breakfast approximately 25 minutes prior to administration of study drug. The breakfast will be consumed approximately over a 20-minute period with the study drug administered within approximately 5 minutes of completion of the meal. There are no water restrictions prior to dosing for subjects dosed under fed conditions. . The study medication should be administered with ambient temperature water to a total volume of approximately 240 mL (8 fluid ounces) per dosing bottle. No food will be allowed for at least 4 hours post dose. The breakfast will be a high-calorie / high fat meal consisting of 2 eggs fried in butter, 2 strips of bacon or 50 g of meat or sausage, 2 slices of toast with butter, 4 ounces of hash brown potatoes and 8 ounces of whole milk. Investigational Medical Products Administered Participants will receive either compound or matching placebo. A description of the IMPs is provided in Table 4. Table 4: Investigational Medicinal Products Abbreviations: HDPE = high-density polyethylene; IMP = investigational medicinal product; MAD = multiple ascending dose; SAD = single ascending dose; TBD = to be determined. aTwo dosage strengths (15 and 100 mg) of placebo capsules will be provided. The 15 mg placebo capsule will be used for the 1, 5, and 25 mg compound capsules, and the 100 mg placebo capsule will be used for 100 mg compound capsules. bPlanned doses. Doses may be adjusted based on safety and tolerability assessments and emerging pharmacokinetic data. Doses for the MAD portion will be determined based on the results of the SAD portion of the study and may be adjusted based on ongoing assessments. This is an open-label, single-dose, biomarker study of the compound in participants aged 18 years and older with a diagnosis of mild cognitive impairment (MCI) due to AD or mild AD according to the 2018 National Institute on Aging and Alzheimer’s Association (NIA-AA) criteria which requires biomarker evidence of amyloid pathology (Stages 3 and 4 per FDA draft guidance for industry on Early Alzheimer’s Disease: Developing Drugs for Treatment, March 2024). Participants must have a MMSE score of 18 to 30 (inclusive). Approximately 10 patients with Alzheimer’s disease may be enrolled. Pharmacodynamic biomarker endpoints may include concentrations of soluble TREM2 (sTREM2) in the CSF to investigate the compound target engagement in the central compartment, and other exploratory biomarkers (e.g., soluble colony-stimulating factor 1 receptor [sCSF1R], osteopontin) to assess PD. Genetic Testing (AD Cohort, Part C only) Approximately 5 mL of whole blood sample will be collected for genetic testing (APOE, TREM2 and other dementia risk genes) at Screening to confirm that the subject is eligible for the study. Participants who have genetic results for genes of interest available in their records will not be required to be genetically tested again. MMSE (AD Cohort, Part C only) The Mini-Mental State Examination (Folstein, 1975) is a 30-point questionnaire that is used to assess cognitive impairment (dementia and the severity of cognitive impairment) and that can be used to follow the course of cognitive changes in an individual over time. It includes tests of orientation, attention, memory, language, and visual-spatial skills. The range for the total MMSE score is 0 to 30, with lower scores indicating greater levels of impairment. The investigator will complete the MMSE at the Screening Visit. Subjects must have an MMSE score of 18 to 30, inclusive, for enrollment in the study. MRI (AD Cohort, Part C only) An MRI scan will be obtained at Screening and Day 7 to ensure eligibility and follow-up monitoring of subjects. The following MRI sequences will be obtained at Screening and Day 7 Visits: T1 (without contrast), T2, T2 fluid-attenuated inversion recovery (T2-FLAIR), T2* GRE, Diffusion- weighted. Amyloid testing (AD Cohort, Part C only) Approximately 10 mL of blood sample will be collected and tested (central lab) to confirm evidence of amyloid pathology at Screening. Justification for Dose SAD Portion (Part A) The proposed clinical starting dose is based upon results of GLP toxicity studies that have been performed in rats and nonhuman primates, and the predicted sTREM2 response in humans, which is based on the available PK / PD studies in nonhuman primates. Based on this, a pharmacologically active dose (PAD) approach (described below) was used, which produces a lower starting dose. The primary model for predicting potential compound-mediated human pharmacology is based on the observed changes in CSF sTREM2 levels after single-dose administration in male nonhuman primates. In 2 studies, nonhuman primates were given single doses of the compound ranging from 0.1 to 25 mg / kg, and systemic concentrations of the compound and CSF concentrations of sTREM2 were measured. Given the (intended) potential for target-mediated pharmacology, particularly after a prolonged period of target engagement, the modeled sTREM2 response was used to estimate a dose that may be associated with minimal human pharmacological effect. The reduction of sTREM2 in human CSF after single compound doses can be predicted using the nonhuman primate model estimates and the lowest predicted clearance. Preliminary exposures observed for the 2 mg starting dose and the subsequent 6 mg and 18 mg doses administered to date in the SAD portion of the study are shown in Table 5 below, along with the safety factors and projected exposures for the remaining planned doses in this study.

[0013] Table 5: Plasma Exposure of Compound After Administration of Single Doses of the Compound to Healthy Adult Participants, wherein “A” refers to a safety margin of between 1 and 20-fold; “B” refers to a safety margin of between 20 and 50-fold; “C” refers to a safety margin of between 50 and 100-fold; and “D” refers to a safety margin of greater than 100-fold. These exposure limits were calculated based on the highest dose (27 mg / kg / day) in male nonhuman primates without adverse-related effects, with a 10-fold safety margin applied. If less than proportional increases in exposures are observed due to saturation of absorption, remaining escalations may be performed under fed conditions. Simulations of the food effect based on previously completed cohorts in the fasted stated will be used to ensure that the projected exposures under the fed state will not exceed the exposure limits. MAD Portion (Part B) The doses that are chosen for the MAD portion of the study will be based on emerging safety and PK data from the SAD portion of the study. All doses that are administered in the MAD cohorts will have been previously shown to be well tolerated in healthy adult participants when administered as a single dose in the SAD portion of the study, and the projected mean exposure (based on steady-state Cmax or AUC0-tau) will not exceed the mean exposures that have been observed at the doses in the SAD portion of the study. AD Portion (Part C) A single oral dose of compound will be administered in AD patients. The dose that is chosen for this AD portion of the study will be based on review of available safety, PK and PD data from the SAD portion of the study. The dose administered in the AD cohort will have been previously shown to be safe, well tolerated and shown to have an effect on biomarkers in healthy adult participants when administered as a single dose in the SAD portion of the study. Results The SAD / MAD trial assessed the safety, tolerability, PK, and PD of a compound of Formula (I) disclosed herein across 14 cohorts. The trial enrolled a total of 115 participants, in which 104 participants were healthy volunteers and 11 participants were AD patients. For the 104 healthy volunteers in SAD / MAD cohorts,eight SAD cohorts of healthy volunteers administered up to a 140 mg dose and four MAD cohorts of healthy volunteers administered up to a 50 mg dose were evaluated. The trial also included an elderly cohort and a single dose cohort of 11 AD patients, including some participants who carry TREM2 or other genetic risk factors for AD. Eighty-nine (89) participants received the compound of Formula (I) disclosed herein, including 34 who were 55 years of age and older. The compound of Formula (I) disclosed herein was generally considered safe and well tolerated acoss all cohorts. No serious adverse effects (AE) or drug interruption / study discontinuations due to AE occurred. No clinically meaningful abnormalities in vital signs or ECGs (electrocardiogram) occurred. Additionally, protocol-specified stopping criteria were not met. Phase I Trial Results for SAD Cohorts Safety and Tolerability Table 6 shows the safety and tolerability assessment of the Phase I trial with the compound of Formula (I) disclosed herein in SAD cohorts. Seven cohorts of healthy volunteers (HV) and one cohort of patients with Alzheimer’s Disease (AD) were administered a placebo or a compound of Formula (I) disclosed herein at a single dose at 2 mg, 6 mg, 18 mg, 36 mg, 72 mg, or 140 mg. The results suggest favorable safety and tolerability for single doses up to 140 mg in volunteers and 72 mg in patients with Alzheimer’s disease. No serious adverse effects were observed in SAD cohort and the AD cohort. Additionally, no study or study drug was discontinued due to adverse effects. Table 6. Compound of Formula (I) Phase I Safety and Tolerability: SAD Cohort aEvents determined by the investigator to be “related” to the study drug.bHeadache (mild). AD, Alzheimer’s disease; AE, adverse event; OL, open label; SAD, single-ascending dose. Phase I Trial Results for MAD Cohorts Safety and Tolerability Table 7 shows the safety and tolerability assessment of the Phase I trial with the compound of Formula (I) disclosed herein in MAD cohorts. Five multiple ascending dose (MAD) cohorts of healthy volunteers (HV) were administered a placebo or the compound of Formula (I) disclosed herein at 6 mg, 12 mg, 25 mg, or 50 mg once daily for 14 days. One eldery MAD cohort of healthy volunteers was also administered a compound of Formula (I) disclosed herein at 25 mg daily for 14 days. No serious adverse effects were observed in the MAD cohort. Additionally, no study or study drug was discontinued due to adverse effects. Events in treatment-related adverse effects, such as the increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), nausea, pain, headache, decrease in platelet count, and rhabdomyolysis, were also evaluated. The combined results suggest favorable safety and tolerability for multiple doses up to 50 mg in healthy volunteers. Table 7. Compound of Formula (I) Phase I Safety and Tolerability: MAD Cohort aEvents determined by investigator to be “related” to study drug.bPresented as a mild, asymptomatic, transient elevation in serum creatine kinase that resolved without medical intervention (AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyltransferase; MAD, multiple-ascending dose). Conclusion of Phase I Trial Results for SAD and MAD Cohorts The keypoints of Phase I single and multiple ascending dose (SAD / MAD) trial are summarized below: . The Phase 1 trial provided a comprehensive and robust dataset evaluating healthy volunteers, elderly participants and a cohort of AD patients. . Compound of Formula (I) described herein demonstrated a favorable safety and tolerability profile across all cohorts with no serious adverse events. . All treatment-related adverse events (AEs) were mild or moderate and self-resolving. . Compound of Formula (I) described herein showed a predictable and dose-dependent pharmacokinetic (PK) profile that supports once-daily dosing. These data demonstrated that the compound of Formula (I) described herein has high CNS penetrance with an estimated cerebral spinal fluid (CSF) to unbound plasma ratio of 0.91. . PK and sTREM2 reduction observed in the single dose AD cohort was consistent with healthy volunteers and the reduction in sTREM2 was similar across evaluated TREM2 and ApoE genetic variants supporting development in AD across genotypes. . PK and sTREM2 reduction observed in the multiple ascending dose (MAD) elderly cohort was consistent with healthy volunteers. . At the 25 mg dose, the compound of Formula (I) described herein achieved the maximum sTREM2 reduction in the CSF of approximately 50%. . PK / PD data support the selection of a 25 mg once-daily oral dose for the Phase 2 trial in AD patients. A number of embodiments of this invention have been disclosed and it is apparent that the basic examples may be altered to provide other embodiments that utilize the compounds and methods of this invention. Therefore, it will be appreciated that the scope of this invention is to be defined by the application and claims rather than by the specific embodiments that have been represented by way of example.

Claims

WHAT IS CLAIMED IS:

1. A method of treating Alzheimer’s Disease in a subject in need thereof, the method comprising administering to the subject a dosage of about 0.5 mg to about 400 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

2. The method of claim 1, wherein the dosage is about 1 mg to about 400 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

3. The method of claim, wherein the dosage is about 2 mg to about 400 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

4. The method of claim 1, wherein the dosage is about 0.5 mg to about 140 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

5. The method of claim 1, wherein the dosage is about 0.5 mg to about 100 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

6. The method of claim 1, wherein the dosage is about 0.5 mg to about 80 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

7. The method of claim 1, wherein the dosage is about 0.5 mg to about 60 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

8. The method of claim 1, wherein the dosage is about 0.5 mg to about 40 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

9. The method of claim 1, wherein the dosage is about 0.5 mg to about 20 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

10. The method of claim 1, wherein the dosage is about 0.5 mg to about 10 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

11. The method of claim 1, wherein the dosage is about 1 mg, about 2 mg, about 6 mg, about 18 mg, about 36 mg, about 72 mg, or about 140 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

12. The method of claim 1, wherein the dosage is about 6 mg, about 12 mg, about 25 mg, or about 50 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

13. The method of claim 1, wherein the small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof is orally, intravenously, or subcutaneously administered to the subject.

14. The method of claim 13, wherein the small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof is orally administered to the subject.

15. The method of claim 14, wherein the small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof is orally administered to the subject as a tablet, chewable tablet, minitablet, caplet, pill, bead, hard capsule, soft capsule, gelatin capsule, granule, powder, lozenge, patch, syrup, flavored syrup, or juice.

16. The method of claim 15, wherein the small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof is orally administered to the subject as a tablet, hard capsule, soft capsule, or gelatin capsule.

17. The method of claim 1, wherein the small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof is administered daily, weekly, biweekly, or monthly.

18. The method of claim 17, wherein the small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof is administered daily.

19. The method of claim 18, wherein the small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof is administered once or multiple times daily.

20. The method of claim 19, wherein the small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof is administered once or twice daily.

21. The method of claim 1, wherein the small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof is administered once daily.

22. The method of claim 1, wherein the subject has a mutation in TREM2.

23. The method of claim 1, wherein the subject has one or more of R47H, R62H, H157Y, D87N, T96K, or L211P variants of TREM2.

24. The method of claim 1, wherein the subject has one or more microglia-associated Alzheimer’s Disease risk gene variants.

25. The method of claim 24, wherein the one or more microglia-associated Alzheimer’s Disease risk gene variants is APOE4, MS4A, CD33, CLU, INPPSD, or CR1.

26. The method of claim 1, wherein the subject has been identified and / or diagnosed as having Alzheimer’s Disease.

27. The method of claim 1, wherein the subject has a diagnosis of mild cognitive impairment due to Alzheimer’s Disease.

28. The method of claim 1, wherein the subject has a diagnosis of mild Alzheimer’s Disease according to the 2018 National Institutes on Aging and Alzheimer’s Association criteria.

29. The method of claim 1, wherein the subject has a MMSE score of 18 to 30 (inclusive).

30. The method of claim 1, wherein the subject is asymptomatic for Alzheimer’s Disease.

31. The method of claim 1, wherein the small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof is administered to the subject prior to the onset of signs or symptoms of Alzheimer’s Disease.

32. The method of claim 1, wherein the subject is aged 18 years or older.

33. The method of claim 1, wherein the small molecule TREM2 agonist is a compound of Formula (I):or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein Ring A together with the 6-membered ring system to which it is fused forms a bicyclic ring system selected from:Ring B is selected from:wherein X1is CR10or N; X2is C(R10)2, O, C(=O), S(O)2, or NR10; X3is CR10or N; X4is CR10or N; X5is CR10or N; X6is CR10, N, or NR10; X7is CR10or N; X8is CR10or N; X9is CR10or N; X10is CR10, C(R10)2, O, S or NR10; X11is C or N; X12is CR10or NR10; X13is C or N; X23is CR10, N, NR10, SO2, or C=O; X24is CR10, N, NR10, SO2, or C=O; X25is CR10, N, NR10, SO2, or C=O; L is a bond or an optionally substituted straight chain or branched C1-6 alkylene; wherein the straight chain or branched C1-6 alkylene is optionally substituted with C1-6 alkyl, hydroxyl, or -N(RB)(RC); R1aand R1bis each independently H, C1-6 alkyl, or C1-6 heteroalkyl; R2aand R2bis each independently H, D, C1-6 alkyl, C1-6 haloalkyl, C1-6 heteroalkyl, C3-8 cycloalkyl, or C3-8 heterocyclic; R3is H, D, C1-6 alkyl, or C1-6 heteroalkyl; or R1a, R1b, and R3are taken together with their intervening atoms to form a cyclic group selected from a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring;R4is C1-6alkyl, C2-6alkenyl, C1-6haloalkyl, C1-6heteroalkyl, C3-8cycloalkyl, C3-8heterocycloalkyl, aryl, heteroaryl, -O(RA), -N(RB)(RC), C(=O)(C1-6alkyl), -C(=O)O(C1-6alkyl), - C(=O)(cycloalkyl), -C(=O)(heterocyclic), or -C(=O)(heteroaryl), wherein alkyl, alkenyl, haloalkyl, heteroalkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl are optionally further substituted with 1-6 R11; R5is C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C1-6 heteroalkyl, C3-8 cycloalkyl, C3-8 heterocyclic, aryl, heteroaryl, halogen, cyano, -O(RA), -N(RB)(RC), C(=O)(C1-6alkyl), - C(=O)O(C1-6alkyl), -C(=O)(cycloalkyl), -C(=O)(heterocyclic), or -C(=O)(heteroaryl), wherein alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl are optionally further substituted with 1-6 R11; R6and R7are each independently H, D, C1-6alkyl, C2-6alkenyl, C1-6heteroalkyl, C1-6haloalkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, halogen, cyano, -O(RA), or -N(RB)(RC), wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclic, aryl, and heteroaryl is optionally substituted with one or more R12; or wherein the R6and R7groups together with the carbons to which they are attached form a 5- membered heterocyclic group; R8aand R8bare each independently H or C1-6 alkyl; or R8aand R8bare taken together with their intervening atoms to an oxo group; R9is H or C1-6 alkyl; R10is H, C1-6 alkyl, C1-6 heteroalkyl, C1-6 haloalkyl, heteroaryl, halogen, cyano, - O(RA), -N(RB)(RC), or -N(RB), wherein heteroaryl is optionally further substituted with 1-6 R11, or wherein any two R10groups together with the carbons to which they are attached at X23, X24, or X25form a 5-membered heterocyclic group; R11and R12are each independently H, D, C1-6 alkyl, C1-6 heteroalkyl, C1-6 haloalkyl, halogen, oxo, -O(RA), or -N(RB)(RC); each RAis independently H, D, C1-6 alkyl, C1-6 heteroalkyl, C1-6 haloalkyl, cycloalkyl, heterocyclic, or -N(RB)(RC); each RBand RCis independently H, C1-6 alkyl, C1-6 heteroalkyl, C1-6 heteroaralkyl, C1-6 haloalkyl, cycloalkyl, heterocyclic, or -C(O)-alkyl, wherein the C1-6 alkyl or heterocyclic is optionally further substituted with cycloalkyl or –O(RA);R13is an optionally substituted C1-6aliphatic group, halogen, -OR, -CN, -NR2, -C(=O)R, -C(=O)OR, -C(=O)NR2, -SO2R, -SO2NR2, C1-6haloalkyl, or C1-6haloalkoxy; n is 0, 1, or 2; and m is 0, 1, or 2.

34. The method of claim 33, wherein the small molecule TREM2 agonist is a compound of Formula (II):tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in claim 33.

35. The method of claim 1, wherein the small molecule TREM2 agonist is a compound of Formula (II):tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein X1is CR10or N; X2is C(R10)2 or O; R2aand R2bis each independently H, D, methyl,, , ; R3is H or D;R6is H, methyl, propyl,R7is methyl,36. The method of claim 33, wherein the small molecule TREM2 agonist is a compound of Formula (III):tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in claim 33.

37. The method of claim 33, wherein the small molecule TREM2 agonist is a compound of Formula (IV):tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in claim 33.

38. The method of claim 33, wherein the small molecule TREM2 agonist is a compound of Formula (V):tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in claim 33.

39. The method of claim 33, wherein the small molecule TREM2 agonist is a compound of Formula (VI):tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in claim 33.

40. The method of claim 33, wherein the small molecule TREM2 agonist is a compound of Formula (VII):tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in claim 33.

41. The method of claim 33, wherein the small molecule TREM2 agonist is a compound of Formula (VIII):tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in claim 33.

42. The method of claim 33, wherein the small molecule TREM2 agonist is a compound of Formula (IX):tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in claim 33.

43. The method of claim 33, wherein the small molecule TREM2 agonist is a compound of Formula (X):tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in claim 33.

44. The method of claim 33, wherein the small molecule TREM2 agonist is a compound of Formula (XI):tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in claim 33.

45. The method of claim 33, wherein the small molecule TREM2 agonist is a compound of Formula (XII):tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in claim 33.

46. The method of claim 33, wherein the small molecule TREM2 agonist is a compound of Formula (XIII):tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in claim 33.

47. The method of claim 33, wherein the small molecule TREM2 agonist is a compound of Formula (XIV):tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer, wherein each variable is as defined above in claim 33.

48. The method of claim 1, wherein the small molecule TREM2 agonist is a compound selected from Table A, or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or the tautomer.

49. The method of claim 1, wherein the dosage is about 2 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

50. The method of claim 1, wherein the dosage is about 6 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

51. The method of claim 1, wherein the dosage is about 10 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

52. The method of claim 1, wherein the dosage is about 12 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

53. The method of claim 1, wherein the dosage is about 18 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

54. The method of claim 1, wherein the dosage is about 25 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

55. The method of claim 1, wherein the dosage is about 36 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

56. The method of claim 1, wherein the dosage is about 50 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

57. The method of claim 1, wherein the dosage is about 72 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

58. The method of claim 1, wherein the dosage is about 140 mg of a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof.

59. The method of claim 1, wherein after being administered the compound of Formula (I) disclosed herein once daily for 14 days, the subject exhibits at least a 10% decrease in the concentrations of soluble TREM2 (sTREM2) in the CSF after administration as compared with the levels prior to administration of the compound.

60. The method of claim 1, wherein after being administered the compound of Formula (I) disclosed herein once daily for 14 days, the subject exhibits a 70%, a 65%, a 60%, a 55%, a 50%, a 45%, a 40%, a 35%, a 30%, a 25%, a 20%, a 15%, or a 10% decrease in the concentrations of sTREM2 in the CSF as compared with the levels prior to administration of the compound.

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