Agents and methods for treating tauopathies

Abstract

Disclosed are agents that include a) a binding and / or disaggregating moiety that adheres to a target polypeptide in its amyloid fibril form, and proceed to inhibit the target protein and / or disaggregate the fibril form, and b) a nanomass moiety that promotes transfer of the agent to a site of the target polypeptide. The disclosed agents can be used in methods for destabilizing a tau amyloid fibril, and for treating a tauopathy (e.g., Alzheimer's disease, progressive supranuclear palsy) in a subject.

Description

[0001]AGENTS AND METHODS FOR TREATING TAUOPATHIES CROSS REFERENCE TO RELATED APPLICATIONS This application claims the benefit under 35 U.S.C. Section 119(e) of co- pending and commonly-assigned U.S. Provisional Patent Application No.63 / 633,985, filed April 15, 2024, entitled “AGENTS AND METHODS FOR TREATING TAUOPATHIES”, the contents of which is incorporated by reference herein. STATEMENT OF RIGHTS This invention was made with government support under AG070895, awarded by the National Institutes of Health. The government has certain rights in the invention. BACKGROUND Alzheimer’s disease (AD) is one among dozens of neurological disorders that are driven by aggregation of functional protein monomers into pathological fibrillar aggregates called “amyloid.” Owing to their extreme stability and self-reproducing nature, amyloids persist in brains once formed, multiply, and spread from cell to cell, killing neurons and thereby causing dementia or movement disorders. Tau amyloid fibrils are now indicated to be more closely related with cognitive symptoms in AD than amyloid-beta. (Arriagada et al., 1992; Bierer et al., 1995; Joie et al.2019). Because of the association of fibrils with disease, there have been several attempts at delaying and preventing aggregation of tau and promoting clearance of tau amyloid fibrils. Owing to frustration from inability to effectively target amyloids with small molecules, pharmaceutical companies have almost entirely shifted drug discovery efforts from small molecule programs to the development of biologics, such as antibodies, for targeted inhibition of amyloids. The limitation of biologics, especially antibodies, is that they have little ability to penetrate the blood- brain barrier and cell membranes to reach cell interiors, the location of important amyloid targets. As an additional problem, antibodies are extremely expensive to produce, which limits their potential impact on the general population, since billions of aging people are expected to require anti-amyloid therapies. As a result, it is unlikely that antibody production will meet the desired criteria as a robust and economical anti-amyloid treatment. Whereas compounds with in vitro anti-amyloid activity are known, none are proven clinical therapeutics, often lacking in vivo efficacy for reasons including limited bioavailability, poor metabolic stability, poor drug-like properties, and lack of specificity. Therefore, there is a need in the field for improved agents for treating amyloid diseases, especially tauopathies. SUMMARY OF THE INVENTION In some aspects, the disclosed agents comprise a) a binding and / or disaggregating moiety that adheres to a target polypeptide in its amyloid fibril form, and proceeds to inhibit the target protein and / or disaggregate the fibril form, and b) a nanomass moiety that promotes transfer of the agent to a site of the target polypeptide. In some embodiments, the binding and / or disaggregating moiety is a peptidic compound that inhibits aggregation of the target polypeptide and / or disassembles a target polypeptide aggregate, and the nanomass moiety comprises a magnetic nanoparticle, wherein the target polypeptide comprises a protein sequence within an amyloid fibril. In some embodiments, the peptidic compound comprises one or more D- amino acid residues. In some embodiments, the target polypeptide is a tau amyloid fibril. In some embodiments, the peptidic compound is selected from D-TLKIVWC (SEQ ID NO: 2) (DP), D-TLKIWWX1 (SEQ ID NO: 3) , wherein X1 is a single D- amino acid reissue or a string of D-amino acid residues, D-TWKLVLC (SEQ ID NO: 4) , D-YVIIERC (SEQ ID NO: 5) , D-DYYFEFC (SEQ ID NO: 6) , L-SVWIWYE (SEQ ID NO: 7) , L-DVQMINKKLK (SEQ ID NO: 8) , and a combination thereof. In some embodiments, the peptidic compound comprises D-TLKIVWX2 (SEQ ID NO: 9) , wherein X2 is a single D-amino acid selected from alanine (A), serine (S), isoleucine (I), valine (V), arginine (R), lysine (K), glutamic acid (E), Aspartic Acid (D), proline (P) and threonine (T). In some embodiments, the magnetic nanoparticle comprises a coating that comprises polyethylene glycol (PEG), dextran, starch, chitosan, lipid, citrate, polyaniline, meso-2,3-dimercaptosuccinic acid, poly(maleic anhydride-alt-1- octadecene), polyacrylamide, phosphonate, silica, a protein or a peptide segment having a sequence that is recognized by membrane-embedded proteins in the brain endothelium for conveying the agent across the blood-brain barrier, or a combination thereof. In some embodiments, the dextran comprises dextran-20kDa, dextran-40kDa, carboxy dextran, cross-linked dextran-20kDa, or a combination thereof. In certain embodiments, the magnetic nanoparticle is an iron oxide nanoparticle (IONP). In certain embodiments, the nanoparticle has a hydrodynamic particle size from about 4 nanometers to about 200 nanometers as measured by dynamic light scattering. In some embodiments, the agent destabilizes a tau amyloid fibril when in contact with said tau amyloid fibril. In some embodiments, the agent is permeable across the blood-brain barrier. In certain aspects, the disclosed compositions comprise one or more of the agents described above and in the rest of the disclosure. Such compositions, in some embodiments, are effective in treating a condition associated with polypeptide aggregation. Such compositions, in some embodiments, are effective in treating a condition associated with tau protein fibrillation. In certain aspects, the disclosed compositions further comprise a pharmaceutically acceptable excipient. In some embodiments, the excipient increases membrane permeability to peptides. In certain aspects, the disclosed methods of preparing one or more of the agents described above and in the rest of the disclosure comprise reacting a dextran coated magnetic nanoparticle coupled to at least one –COOH group with maleimide- CH2-NH2in presence of N-ethyl-N′-(3-(dimethylamino)propyl)carbodiimide (EDC) and N-hydroxysulfosuccinimide (Sulfo-NHS), thereby forming a maleimide-magnetic nanoparticle, and reacting the maleimide-magnetic nanoparticle with a peptidic compound comprising one or more D-amino acid residues and a C-terminal cysteine, thereby forming the agent. In some aspects, the disclosed methods of treating or preventing a condition associated with polypeptide aggregation in a subject in need thereof comprise administering to the subject an effective amount of one or more agents described above and in the rest of the disclosure, or a composition that comprises one or more of the agents described above and in the rest of the disclosure, thereby treating or preventing the condition. In some embodiments, the condition is associated with tau protein fibrillation. In some embodiments, the agents and compositions described herein are administered intravenously, intranasally, or intramuscularly. In some embodiments, the condition comprises Alzheimer's disease. In other embodiments, the condition comprises progressive supranuclear palsy, which is shown also to be sensitive to treatment with EGCG, or chronic traumatic encephalopathy, which is structurally related to AD-tau fibrils that contain the EGCG binding cavity that is described here, or other tauopathy. In some embodiments, the subject is a human. In some aspects, the disclosed methods for diagnosing a condition associated with polypeptide aggregation in a subject in need thereof, comprise administering the agent described above and in the rest of the disclosure or the composition described above and in the rest of the disclosure to the subject, thereby treating the condition; scanning the subject by a magnetic resonance imaging (MRI) spectroscopy to get an MRI scan; and diagnostically processing the MRI scan derived from magnetic resonance imaging (MRI) spectroscopy. In some embodiments, the diagnosed condition is associated with tau protein fibrillation. In some embodiments, the agents and compositions described herein for diagnosing are administered intravenously, intranasally, or intramuscularly. In some embodiments, the diagnosed condition comprises Alzheimer's disease. In other embodiments, the diagnosed condition comprises progressive supranuclear palsy, which is shown also to be sensitive to treatment with EGCG, or chronic traumatic encephalopathy, which is structurally related to AD-tau fibrils that contain the EGCG binding cavity that is described here, or other tauopathy. In some embodiments, the subject is a human. In some embodiments, the disclosed method of destabilizing a tau amyloid fibril, includes contacting the tau amyloid fibril with one or more of the agents described above and in the rest of the disclosure. In some aspects, disclosed is a peptidic compound that inhibits aggregation of a target polypeptide, wherein the target polypeptide comprises a zipper sequence, the peptidic compound comprises a binding and / or a disaggregating moiety comprising one or more D-amino acid residues that binds to the target polypeptide in its amyloid fibril state and a delivery moiety comprising a nanoparticle, wherein the peptidic compound comprises at least seven amino acid residues. In some embodiments, the target polypeptide is a tau amyloid fibril. In some embodiments, the peptidic compound is D-TLKIVWC (SEQ ID NO: 2) , D-TLKIVWS (SEQ ID NO: 10) , D- TLKIVWA (SEQ ID NO: 11) , D-TLKIVWD (SEQ ID NO: 12) , or a combination thereof. In certain aspects, the disclosed compositions comprise one or more of the peptidic compounds described above and in the rest of the disclosure. Such compositions, in some embodiments, are effective in treating a condition associated with polypeptide aggregation. Such compositions, in some embodiments, are effective in treating a condition associated with tau protein fibrillation. In certain aspects, the disclosed compositions further comprise a pharmaceutically acceptable excipient. In some embodiments, the excipient increases membrane permeability to peptides. In some aspects, disclosed is a method for treating or preventing a condition associated with polypeptide aggregation in a subject in need thereof, comprising administering the peptidic compound described above and in the rest of the disclosure or the composition described above and in the rest of the disclosure to the subject, thereby treating or preventing the condition. In some embodiments, the condition is associated with tau protein fibrillation. In some embodiments, the agents and compositions described herein are administered intravenously, intranasally, or intramuscularly. In some embodiments, the condition comprises Alzheimer's disease. In other embodiments, the condition comprises progressive supranuclear palsy, which is shown also to be sensitive to treatment with EGCG, or chronic traumatic encephalopathy, which is structurally related to AD-tau fibrils that contain the EGCG binding cavity that is described here, or other tauopathy. In some embodiments, the subject is a human. In some aspects, the disclosed methods for diagnosing a condition associated with polypeptide aggregation in a subject in need thereof, comprise administering the peptidic compound described above and in the rest of the disclosure or the composition described above and in the rest of the disclosure to the subject, thereby treating the condition; scanning the subject by a magnetic resonance imaging (MRI) spectroscopy to get an MRI scan; and diagnostically processing the MRI scan derived from magnetic resonance imaging (MRI) spectroscopy. In some embodiments, the diagnosed condition is associated with tau protein fibrillation. In some embodiments, the agents and compositions described herein for diagnosing are administered intravenously, intranasally, or intramuscularly. In some embodiments, the diagnosed condition comprises Alzheimer's disease. In other embodiments, the diagnosed condition comprises progressive supranuclear palsy, which is shown also to be sensitive to treatment with EGCG, or chronic traumatic encephalopathy, which is structurally related to AD-tau fibrils that contain the EGCG binding cavity that is described here, or other tauopathy. In some embodiments, the subject is a human. In some embodiments, the disclosed method of destabilizing a tau amyloid fibril, includes contacting the tau amyloid fibril with one or more of the agents described above and in the rest of the disclosure. Further embodiments and details for each of these aspects are presented throughout the disclosure. BRIEF DESCRIPTION OF THE FIGURES FIGS.1A and 1B show a covalent complex of a peptide that binds to the target tau amyloid fibrils along with a magnetic nanoparticle. FIG.1A shows a covalent complex of D-TLKIVWC (SEQ ID NO: 2) (DP) with a magnetic nanoparticle (MNP); FIG.1B outlines the two step chemical process for covalent linkage of D-TLKIVWC (SEQ ID NO: 2) to an MNP. S-H represents the sulfhydryl sidechain of Cysteine. FIG.2 is a plot of fluorescence intensity of the amyloid-sensitive dye Thioflavin T (ThT) as a function of time showing that MNPs-DP (i.e. D-TLKIVWC- MNPs (SEQ ID NO: 2)) inhibit fibril formation of tau K18+. Tau K18+ is a recombinant construct of tau comprising residues 244-380, which cover the ordered portion of tau fibrils extracted from AD brains, the negative control (black curve) shows fibril formation of un-inhibited tau K18+. FIGS.3A to 3D present a series of electron micrographs showing that the MNPs-DP can inhibit the aggregation of tau K18+ fibrils and is dose-dependent. FIG. 3A is when tau monomers are incubated alone in vitro. FIG.3B, FIG.3C, and FIG.3D show that the length of the obtained tau fibrils gradually decreases with the increase of MNPs-DP. FIG.3D shows that a lot of spherical structures are observed at the high concentration of MNPs-DP. FIGS.4A to 4D (a series of fluoroscence microscope images) and FIG.5 show that the products of disaggregated tau fibrils extracted from AD brains do not seed the formation of tau fibrous aggregates in tau biosonsor cells. Biosensor cells overexpress a flourescently labeled tau K18. FIG.4A shows the biosensor cells without tau seeding. FIG.4B shows when tau fibrils are introduced into these cells with the aid of lipofectamine, they seed the expressed tau K18 into fibrous aggregates which flourescence, appearing as puncta. This is true of tau fibrils from AD brains. FIG.4C, FIG. 4D, and FIG.5 show that the tau fibrils from AD brains pretreated with D- TLKIVWC-MNPs (SEQ ID NO: 2) do not seed the biosensor cells. The significance of this result is that the products of disaggregated tau fibrils from AD brain do not appear to support tau seeding, often called prion-like spreading. Prion-like spreading is the process by which tau pathology spreads through the brain. This experiment suggests that the complex or agents described herein are not likely to stimulate spread of tau pathology in brains. Note: in FIG.5 the pink and green results on the right refer to AD-tau fibrils pre-treated with MNPs-DP. FIG.6 is a plot of fluorescence intensity of the amyloid-sensitive dye Thioflavin T as a function of time showing that MNPs-DP disaggregates recombinant tau K18+ fibrils, the black curve is the negative control—untreated tau K18+ fibrils. It shows that MNPs-DP retains the property of DP to diasggregate tau K18+ fibrils (red and green curves), which has a more powerful property than the original 6-residue D- TLKIVW (SEQ ID NO: 13) peptide (blue curve) that can inhibit growth of fibrils but not disaggregate them. FIGS.7A to 7D show a series of electron micrographs demonstrating that DP alone can disaggregate tau K18+ fibrils while the naked MNPs cannot. So the MNPs- DP retains the property of the DP to disaggregate tau K18+ fibrils. FIG.7A is when tau K18+ fibrils are incubated alone without any treatment; FIG.7B shows that MNPs- DP can disaggregate tau K18+ fibrils; FIG.7C shows that MNP alone cannot disaggregate tau K18+ fibrils; FIG.7D shows that DP alone can disaggregate tau K18+ fibrils. FIGS.8A to 8D (a series of electron micrographs) and FIG.9 show that the DP and MNPs-DP can disaggregate tau fibrils extracted from humn AD autopsied brains; FIG.8A shows tau fibrils extracted from the AD brain; FIG.8B shows the AD tau fibrils after incubation with DP (500 µM) for two days, demonstrating that the DP peptide (D-TLKIVWC (SEQ ID NO: 2) ) alone is very effective in desaggregation; FIG.8C shows the tau fibrils from the AD brain after incubated with naked MNPs (0.05 mg / ml) for two days; FIG.8D shows the tau fibrils from the AD brain incubated with MNPs-DP (0.05 mg / ml) for two days. FIG.9 is a graphical representation of FIG.8 results. FIG.10 shows the dot blot experiment demonstrating that the fibril content of the AD brain samples are decreased after the incubation with DP or DP nanoparticles (MNPs-DP). FIG.11 demonstrates that PS19 mice (which express the tau P301S mutation found in tauopathies and which experience nueronal loss and accumulation of tau fibrils) do not lose appreciable weight when injected in their tail veins with standard phospho- buffered saline solution, MNPs, or D-TLKIVWC (SEQ ID NO: 2) -MNPs whithin ten weeks. This experiment is partial evidence of the safety of MNPs, and D-TLKIVWC (SEQ ID NO: 2) -MNPs. FIGS.12A and 12B illustrate the Barnes maze test of spatial learning and memory for assesing the efficacy of treatment of PS19 mice by tail vein injection of D- TLKIVWC (SEQ ID NO: 2) -MNPs. FIG.12 A illustrates the setup for the Barnes test. A disk with diameter of ~ 120 cm contains 20 equally spaced mouse-sized holes near the periphery. 19 of these are blocked; 1 hole leads to an “escape box” in which the mouse can shelter to escape unpleasant bright lights and loud static noise (see inset). Each mouse is timed and tracked as it seeks the escape box. Clues to the location of the escape box are provided by colored patches posted on orthogonal walls of the enclosure. The experiment is carried out over 6 days. On Day 1, each mouse is habituated to the aparatus by being placed on the disk for 3 minutes. On Days 2-5, mice are each given 3 training sessions of 2 minutes to find the escape box as cued by the colored patches. On Day 6, memory is tested: each mouse is placed on the disk and timed and tracked as it finds the escape box. FIG.12B shows that all group mice gradually acquired the task because the time that they need to find the escape box is decreasing, but the PS19 mice treated with PBS (salt solution) or with naked MNPs take longer times to learn the task. The performance PS19 mice injected with MNPs-DP are comparable with the wild-type (WT) control mice, indicating the MNPs-DP treatment can improve the learning ability of the PS19 mice. FIGS.13A to 13D show the experiments that suggest D-TLKIVWC (SEQ ID NO: 2) -MNP (labeled MNPs-DP) injections rescue memory deficits of PS19 tauopathy mice: FIG.13A is a histogram showing the time in seconds for mice to first find the escape box hole. Notice that wild type (WT) mice perform better than the PS19 mice. PS19 mice treated with PBS (salt solution) perform the least well. PS19 mice treated with MNPs-DP perform best. FIG.13B is a histograpm showing how many times the mice come to the target hole. The WT mice perform better than the PS19 mice, but PS19 mice treated with MNPs-DP perform almost as well as as WT mice. PBS-treated PS19 mice perform poorly. The same pattern of results is observed for how long mice spend at the target hole (FIG.13C) and the total distance mice travel near the target hole (FIG. 13D). In short, all four measures suggest that injected D-TLKIVWC (SEQ ID NO: 2) - MNPs rescue memory deficits of AD mice. This is consistent with the in vitro and cell experiments detailed in earlier slides that D-TLKIVWC (SEQ ID NO: 2) -MNPs inhibite tau aggregation and disaggregate toxic tau fibrils. FIGS.14A and 14B show the rotarod test for mice to resist falling from a rotating rod. Mice are placed on an elevated rotating rod and timed for their ability to remain grasped to the rod (FIG.14A), showing the moter function of PS19 mice. FIG. 14B graphs the latency of falling versus days of training, showing the learning ability of PS19 mice to stay on the rotarod. FIG.14A and FIG.14B show that WT mice (black curve) perform significantly better than PBS (salt dolution) treated PS19 mice (red curve). MNPs-DP treated PS19 mice (blue curve) perform as well as WT mice.. FIG.15A and 15B show a graph fluorescence intensity of amyloid-sensitive dye Thioflavin T versus time (hour), when 20 uM tau K18+ monomer were incubated alone or with 5, 10, 20, 50, 100 uM DP / S-DP (D-TLKIVW SEQ ID NO: 13) for 48 h. FIG.15A shows by ThT flourescence, the ability of DP (i.e. D-TLKIVWC (SEQ ID NO: 2) ) to inhibit K18+ fibrils aggregation. FIG.15B shows the effects on tau K18+ fibrils aggregation of D-TLKIVW (SEQ ID NO: 13) (the 6-residue peptide from 2011, here called S-DP). It shows that DP is a better tau-fibril inhibitor than S-DP. FIG.16 is a graph of Thioflavin T fluorescence intensity versus time (hour) showing that that 7-residue D-TLKIVWC (SEQ ID NO: 2) (DP) disaggregates tau K18+ fibrils but 6-residue D-TLKIVW (SEQ ID NO: 13) (S-DP) does not (ThT assay: tau K18+ (20 μM), DP / S-DP (50 μM), ThT (40 μM), DTT (1 mM), heparin (0.225 mg / ml). FIGS.17A to 17D show a series of electron micrographs further illustrating that 7-residue D-TLKIVWC (SEQ ID NO: 2) (DP) disaggregates tau K18+ fibrils but 6- residue D-TLKIVW (SEQ ID NO: 13) (S-DP) does not. FIG.17A shows tau K18+ fibrils incubated ablone; FIG.17B shows that S-DP (D-TLKIVW) does not disaggregate tau K18+ fibrils; FIG.17C and FIG.17D show that DP alone can disaggregate tau K18+ fibrils. FIGS.18A to 18C show dose-dependence of disaggregation of tau K18+ fibrils by D-TLKIVWC (SEQ ID NO: 2) by three measures: FIG.18A by diminished ThT fluorescence showing a graph of fluorescence intensity versus time (hour), FIG.18B by the decrease of fibril content probed by the anti-amyloid OC antibody, and FIG.18C by the decrease of beta-strand content as measured by circular dichroism. FIGS.19A to 19H show a series of negative staining electron micrographs demonstrating the dose-dependence of disaggregation of tau K18+ fibrils by D- TLKIVWC (SEQ ID NO: 2) . FIG.19A is when tau K18+ fibrils are inincubated alone; FIG.19B is when tau K18+ fibrils are treated with 2.5 µM DP; FIG.19C is when treated with 5 µM DP; FIG.19D is when treated with 10 µM DP; FIG.19E is when treated with 20 µM DP; FIG.19F is when treated with 50 µM DP; FIG.19G is when treated with 100 µM DP; and FIG.19H is when treated with 200 µM DP. Notice the length of tau K18+ fibrils decrease and the newly-appearing spherical structures grow larger with increased concentrations of DP. FIGS.20A to 20D show a series of electron micrographs and a graph of fluorescence intensity (a.u.) versus time (hour) demonstrating that D-TLKIVWC (SEQ ID NO: 2) disaggregates human AD-tau fibrils extracted from an autopsied brain, but that D-TLKIVW (SEQ ID NO: 13) does not. FIG.20A (top and bottom) is AD tau fibrils without any treatment; FIG.20B (top and bottom) show that DP alone can disaggregate AD tau fibril; FIG.20C (top and bottom) shows that S-DP (D-TLKIVW (SEQ ID NO: 13) ) does not disaggregate AD tau fibril. FIG.20D is a graph of fluorescence intensity (a.u. = arbitrary units) versus time (hour) showing that D- TLKIVWC (SEQ ID NO: 2) (DP) disaggregates human AD-tau fibrils extracted from an autopsied brain and that D-TLKIVW (SEQ ID NO: 13) (S-DP) does not. FIGS.21A to 21C show a series of fluoroscence microscope images and bar graphs demonstrating that D-TLKIVWC (SEQ ID NO: 2) (DP) at high concentrations inhibit the seeding of human AD-tau extracted from autopsied brain; D-TLKIVW (SEQ ID NO: 13) (S-DP) does not inhibit. That is, the additional residue is necessary for inhibition of tau seeding. FIG.21A shows fluoroscence microscope images of biosensor cells after transfected with DP (top row) and S-DP (bottom row) pre-treated AD tau seeds; FIG 21B shows that D-TLKIVWC (SEQ ID NO: 2) (DP) at high concentrations inhibits the seeding of human AD-tau extracted from autopsied brain; and FIG.21C shows that D-TLKIVW (SEQ ID NO: 13) (S-DP) at high concentrations does not inhibit the seeding of human AD-tau extracted from autopsied brain. FIGS.22A to 22D deomonstrate that neither D-TLKIVWC (SEQ ID NO: 2) (DP) (FIG.22A) nor D-TLKIVW (SEQ ID NO: 13) (S-DP) (FIG.22B) are appreciably toxic to Neuro2a (N2a) cells as judged by the MTT cell viability assay. DP / S-DP are nontoxic to cells, even at the concentration up to 200 uM. FIG.22C demonstrates that D- TLKIVWC (SEQ ID NO: 2) (DP) rescues the toxic effects of tau K18+ monomers whereas D-TLKIVW (SEQ ID NO: 13) (S-DP) is not as effective as DP, as shown in FIG.22D. FIG.23A and 23B demonstrate that the disaggregation products of tau K18+ fibrils produced by D-TLKIVWC (SEQ ID NO: 2) are less toxic than tau oligomers or tau fibrils; FIG 23A shows the cell viability of N2a cells after introducing the disaggregation products of tau K18+ fibrils lead by D-TLKIVWC (SEQ ID NO: 2) (DP), and FIG.23B shows the cell viability of N2a cells after incubation with D-TLKIVW (SEQ ID NO: 13) (S-DP) pre-treated tau K18+ fibirls. FIG.24A and 24B demonstrate that the C-terminal cysteine residue of D- TLKIVWC (SEQ ID NO: 2) is not the sole 7thresidue required for disaggregation of tau K18+ fibrils, and neither redox state of the cysteine sidechain is not required for disaggregation. FIG.24A shows that replacing cysteine with serine (D-TLKIVWS (SEQ ID NO: 10) ), alanine (D-TLKIVWA (SEQ ID NO: 11) ), or aspartate (D-TLKIVWD (SEQ ID NO: 12) ) also disaggregates tau K18+ fibrils, as judged by ThT fluorescence, it also shows that the L-peptide L-TLKIVWC (SEQ ID NO: 20) is relatively ineffective. FIG 24B shows that redox state of the cysteine sidechain does not matter. This experiment suggests that at an all D-peptide of at least a 7-residues improves disaggregation properties. FIG.25 shows data from dot blot studies of AD brain tau fibrils after incubation with H2O, 500 μM D-TLKIVW (SEQ ID NO: 13) (S-DP) and D-TLKIVWX (SEQ ID NO: 14) (X=C,A,S,D,I,V,R,K,E,P,T), respectively. The primary antibody is Anti- Amyloid Fibrils OC Antibody (1:1000). FIG.26 shows quantification of chemiluminescence data from dot blot assay in Fig.25 calculated using FIJI.16 bit using int density. FIG.27 provides electron microscopy images of AD tau fibrils after incubation with H2O, 500 μM D-TLKIVW (SEQ ID NO: 13) (S-DP) and D-TLKIVWX (SEQ ID NO: 14) (X=C,A,S,D,I,V,R,K,E,P,T) for 48 h. FIGS.28A to 28F provide data showing that D-TLKIVWX (SEQ ID NO: 14) shows specificity in disassembling tau fibrils. a, Representative TEM images of tau fibrils extracted from progressive supranuclear palsy brain (PSP tau fibrils) alone and after incubation with 500 μM D-TLKIVWI (SEQ ID NO: 15) for 48 hours. b, Representative TEM images of α-syn fibrils extracted from multiple system atrophy brain (MSA α-syn fibrils) alone and after incubation with 500 μM D-TLKIVWI (SEQ ID NO: 15) for 48 hours. c, Representative TEM images of recombinant α-syn fibrils alone and after incubation with 50 μM D-TLKIVWI (SEQ ID NO: 15) for 24 hours. d, Representative TEM images of wild-type (WT) hnRNPA2 low complexity domain (LCD) fibrils alone and after incubation with 100 μM D-TLKIVWI (SEQ ID NO: 15) for 55 hours. e, ThT assay of 25 μM α-syn fibrils incubated with 50 μM fresh D- TLKIVW (SEQ ID NO: 13) or D-TLKIVWX (SEQ ID NO: 14) (X = C, A, S, D, I, V, R, E, P, T) at 95 h time-point. f, ThT assay of 10 μM WT hnRNPA2 low complexity domain (LCD) fibrils incubated with 100 μM fresh D-TLKIVW (SEQ ID NO: 13) or D-TLKIVWX (SEQ ID NO: 14) (X = C, A, S, D, I, V, R, E, P, T) at 15 h time-point. Scale bars, 0.2 µm. FIGS 29A to 29D provide schematics showing that D-TLKIVWX (SEQ ID NO: 14) (X = I, S, R) peptides form right-handed helical fibrils with conserved steric zipper motifs. a, Representative atomic force microscopy (AFM) image of D- TLKIVWI (SEQ ID NO: 15) fibrils. b-d, Views down the fibril axes (upper row) and perpendicular to the fibril axes (lower row) of the amyloid-like (“mock-amyloid”) fibrils formed by (b) D-TLKIVWI (SEQ ID NO: 15), (c) D-TLKIVWS (SEQ ID NO: 10) , (d) D-TLKIVWR (SEQ ID NO: 16) , as determined by cryo-EM. The conserved steric zipper motifs are represented by grey dotted ellipses. FIGS. 30A to 30D provide schematics showing that D-TLKIVWX (SEQ ID NO: 14) mock-amyloid fibrils form along left-handed AD-tau and drive the fragmentation of AD-tau. a-c, Cryo-EM density, and atomic models of a cross section of PHF fibrils complexed with (a) D-TLKIVWI (SEQ ID NO: 15), (b) D-TLKIVWS (SEQ ID NO: 10) , and (c) D-TLKIVWR (SEQ ID NO: 16) , with views down the fibril axes (upper row) and from the side of the fibril axes (lower row). Details of the PHF structures are evident in sharpened, high-resolution density maps of the PHFs (dark salmon). The D-peptides are visible in unsharpened, low-pass filtered density (7 Å) colored blue (D-TLKIVWI) (SEQ ID NO: 15), marine (D-TLKIVWS (SEQ ID NO: 10) ), and green (D-TLKIVWR (SEQ ID NO: 16) ). The corresponding low-pass filtered density of the PHF is shown in light salmon. Residues Val309-Thr319 are highlighted in yellow in panel a. d, Cryo-EM density, and atomic models of a cross section of PHF fibrils (AD-tau control). FIG.31 provides data showing that the fragmentation of AD-tau after six hours of incubation with 500 μM D-TLKIVWI (SEQ ID NO: 15) was observed using high-speed atomic force microscopy (HS-AFM). The time stamps shown represents the observation time for a random region of the sample. The vulnerable grooves of AD-tau are highlighted by red arrows. Fragments of AD-tau are traced by blue arrows each of length 25 nm. FIGS.32A to 32F provides schematics showing a proposed strain-relief mechanism of disassembly of AD-tau PHF by D-TLKIVWX (SEQ ID NO: 14) peptides. a, Peptide D-TLKIVWX (SEQ ID NO: 14) (blue) is added to left-twisted AD-Tau (red). b, Nucleation of D-TLKIVWX (SEQ ID NO: 14) protofilaments on the surface of AD-tau, where they are constrained to follow the left-twisted conformation of AD-Tau, rather than their natural right-twisted structure. c, Growing segments of the D-TLKIVWX (SEQ ID NO: 14) protofilaments bound to AD-Tau stabilize the complex. d, Fully formed fibrils of left-twisted D-TLKIVWX (SEQ ID NO: 14) experience significant tortional strain (yellow) and strain energy has reached the level of the affinity of adjacent layers of AD-Tau. e, The strain in left-twisted D- TLKIVWX (SEQ ID NO: 14) fibrils is relieved by breaks in both peptide and AD- Tau. f, Fragments of AD-Tau remain bound to fragments of D-TLKIVWX (SEQ ID NO: 14). FIG.33A to 33C provide data showing that L-TLKIVWX (SEQ ID NO: 21) (X = C, I, S, R) all display inferior efficacy in disassembling AD-tau compared to their enantiomers D-TLKIVWX (SEQ ID NO: 14) (Fig.33a,b), despite similar fibril forming ability (Fig.33c). This is because L-peptide principally possesses a left- handed twist, the same as the PHF, and therefore would not produce much torsional strain on the AD-tau. DETAILED DESCRIPTION OF THE INVENTION Embodiments of the invention are discussed in detail below. In describing embodiments, specific terminology is employed for the sake of clarity. However, the invention is not intended to be limited to the specific terminology so selected. A person skilled in the relevant art will recognize that other equivalent parts can be employed and other methods developed without parting from the spirit and scope of the invention. In the context of Alzheimer’s disease (AD), amyloid aggregates of tau are recognized as a cause of the disease. If tau amyloid could be disaggregated, there are strong reasons to believe that the progression of Alzheimer’s disease could be halted. Some challenges to developing compounds or agents that modulate aggregation of polypeptides such as tau are first, to get the agent across the blood-brain-barrier and into neurons where tau aggregates residue, and then to break down the tau aggregates. The US patent 8,754,034, contents of which is incorporated by reference in their entirety, discloses methods to design inhibitory peptides of various types and conformations. Using this method, D-amino acid peptides, such as D-TLKIVW (SEQ ID NO: 13) , D-YVIIER (SEQ ID NO: 17) and D-DYYFEF (SEQ ID NO: 18), can be designed to cap the ends of the structure of the VQIVYK (SEQ ID NO: 19) steric zipper adhesive segment of tau. These peptides can inhibit the formation of aggregates in target proteins such as tau. Disclosed herein are the agents including a) a binding and / or disaggregating moiety that adheres to a target polypeptide in its amyloid fibril form, and proceeds to inhibit the target protein and / or disaggregate the fibril form, and b) a nanomass moiety that promotes transfer of the agent to a site of the target polypeptide . Applicant unexpectedly discovered that a covalent molecular complex of a peptide (for eaxample, D-TLKIVWC (SEQ ID NO: 2) (DP)) liganded to a magnetic nanoparticle (MNP) with properties desirable as both a drug and a diagnostic probe for Alzheimer’s disease. The disclosed peptide binds to fibrils of the protein tau, which form the neurofibrillary tangles of Alzheimer’s disease. Disclosed seven-residue D-peptides can be covalently linked to MNPs to form agents or compelxes, these complexes and the peptide moiety itself actually disassemble (disaggregate) tau fibrils, and to some extent reverse neurological deficits of mice harboring mutant human tau that produce these neurological deficits. Disaggregation include both tau fibrils formed in vitro from recombinantly produced tau, and more importantly, tau amyloid fibrils extracted from autopsied AD brains. The 6-residue D-TLKIVW (SEQ ID NO: 13) does not disaggregate tau fibrils, nor does a scrambled version of D-TLKIVWC (SEQ ID NO: 2) . Applicant unexpectedly discovered that 7-residue peptides, for example, D-TLKIVWC (SEQ ID NO: 2) , disaggregate tau fibrils. In some aspects, the disclosed agents comprise a) a binding and / or disaggregating moiety that adheres to a target polypeptide in its amyloid fibril form, and proceeds to inhibit the target protein and / or disaggregate the fibril form, and b) a nanomass moiety that promotes transfer of the agent to a site of the target polypeptide. In some embodiments, the binding and / or disaggregating moiety is a peptidic compound that inhibits aggregation of the target polypeptide and / or disassembles a target polypeptide aggregate, and the nanomass moiety comprises a magnetic nanoparticle, wherein the target polypeptide comprises a protein sequence within an amyloid fibril. In some embodiments, the peptidic compound comprises one or more D- amino acid residues. In some embodiments, the target polypeptide is a tau amyloid fibril. In some embodiments, the peptidic compound is selected from D-TLKIVWC (SEQ ID NO: 2) (DP), D-TLKIWWX (SEQ ID NO: 3), wherein X is a single D- amino acid reissue or a string of D-amino acid residues, D-TWKLVLC (SEQ ID NO: 4) , D-YVIIERC (SEQ ID NO: 5) , D-DYYFEFC (SEQ ID NO: 6) , L-SVWIWYE (SEQ ID NO: 7) , L-DVQMINKKLK (SEQ ID NO: 8) , and a combination thereof. In some embodiments, the magnetic nanoparticle comprises a coating that comprises polyethylene glycol (PEG), dextran, starch, chitosan, lipid, citrate, polyaniline, meso- 2,3-dimercaptosuccinic acid, poly(maleic anhydride-alt-1-octadecene), polyacrylamide, phosphonate, silica, a protein or a peptide segment having a sequence that is recognized by membrane-embedded proteins in the brain endothelium for conveying the agent across the blood-brain barrier, or a combination thereof. In some embodiments, the dextran comprises dextran-20kDa, dextran-40kDa, carboxy dextran, cross-linked dextran-20kDa, or a combination thereof. In certain embodiments, the magnetic nanoparticle is an iron oxide nanoparticle (IONP). In certain embodiments, the nanoparticle has a hydrodynamic particle size from about 4 nanometers to about 200 nanometers as measured by dynamic light scattering. In some embodiments, the agent destabilizes a tau amyloid fibril when in contact with said tau amyloid fibril. In some embodiments, the agent is permeable across the blood-brain barrier. In certain aspects, the disclosed compositions comprise one or more of the agents described above and in the rest of the disclosure. Such compositions, in some embodiments, are effective in treating a condition associated with polypeptide aggregation. Such compositions, in some embodiments, are effective in treating a condition associated with tau protein fibrillation. In certain aspects, the disclosed compositions further comprise a pharmaceutically acceptable excipient. In some embodiments, the excipient increases membrane permeability to peptides. In certain aspects, the disclosed methods of preparing one or more of the agents described above and in the rest of the disclosure comprise reacting a dextran coated magnetic nanoparticle coupled to at least one –COOH group with maleimide- CH2-NH2 in presence of N-ethyl-N′-(3-(dimethylamino)propyl)carbodiimide (EDC) and N-hydroxysulfosuccinimide (Sulfo-NHS), thereby forming a maleimide-magnetic nanoparticle, and reacting the maleimide-magnetic nanoparticle with a peptidic compound comprising one or more D-amino acid residues and a C-terminal cysteine, thereby forming the agent. In some aspects, the disclosed methods of treating or preventing a condition associated with polypeptide aggregation in a subject in need thereof comprise administering to the subject an effective amount of one or more agents described above and in the rest of the disclosure, or a composition that comprises one or more of the agents described above and in the rest of the disclosure, thereby treating or preventing the condition. In some embodiments, the condition is associated with tau protein fibrillation. In some embodiments, the agents and compositions described herein are administered intravenously, intranasally, or intramuscularly. In some embodiments, the condition comprises Alzheimer's disease. In other embodiments, the condition comprises progressive supranuclear palsy, which is shown also to be sensitive to treatment with EGCG, or chronic traumatic encephalopathy, which is structurally related to AD-tau fibrils that contain the EGCG binding cavity that is described here, or other tauopathy. In some embodiments, the subject is a human. In some aspects, the disclosed methods for diagnosing a condition associated with polypeptide aggregation in a subject in need thereof, comprise administering the agent described above and in the rest of the disclosure or the composition described above and in the rest of the disclosure to the subject, thereby treating the condition; scanning the subject by a magnetic resonance imaging (MRI) spectroscopy to get an MRI scan; and diagnostically processing the MRI scan derived from magnetic resonance imaging (MRI) spectroscopy. In some embodiments, the diagnosed condition is associated with tau protein fibrillation. In some embodiments, the agents and compositions described herein for diagnosing are administered intravenously, intranasally, or intramuscularly. In some embodiments, the diagnosed condition comprises Alzheimer's disease. In other embodiments, the diagnosed condition comprises progressive supranuclear palsy, which is shown also to be sensitive to treatment with EGCG, or chronic traumatic encephalopathy, which is structurally related to AD-tau fibrils that contain the EGCG binding cavity that is described here, or other tauopathy. In some embodiments, the subject is a human. In some embodiments, the disclosed method of destabilizing a tau amyloid fibril, includes contacting the tau amyloid fibril with one or more of the agents described above and in the rest of the disclosure. In some aspects, the disclosed methods for determining the ability of a compound to inhibit fibrillation of a target polypeptide, wherein the target polypeptide includes a zipper-forming sequence susceptible to fibrillation, the method includes: combining the agent of one or more of the agents described above and in the rest of the disclosure with the target polypeptide; measuring the degree of target polypeptide fibrillation; and comparing to a control. In some embodiments, the target polypeptide is tau protein. In some aspects, the disclosed methods for determining the ability of a compound to disaggregate target polypeptide aggregate, wherein the target polypeptide is in its amyloid fibril state, the method includes: combining the agent of one or more of the agents described above and in the rest of the disclosure with the target polypeptide aggregate; measuring the disaggregation degree of target polypeptide assembly; and comparing to a control. In some embodiments, the target polypeptide is tau protein. In some aspects, disclosed is a peptidic compound that inhibits aggregation of a target polypeptide, wherein the target polypeptide comprises a zipper sequence, the peptidic compound comprises a binding and / or a disaggregating moiety comprising one or more D-amino acid residues that binds to the target polypeptide in its amyloid fibril state and a delivery moiety comprising a nanoparticle, wherein the peptidic compound comprises at least seven amino acid residues. In some embodiments, the target polypeptide is a tau amyloid fibril. In some embodiments, the peptidic compound is D-TLKIVWC (SEQ ID NO: 2) , D- TLKIVWS (SEQ ID NO: 10) , D-TLKIVWA (SEQ ID NO: 11) , D-TLKIVWD (SEQ ID NO: 12) , or a combination thereof. In certain aspects, the disclosed compositions comprise one or more of the peptidic compounds described above and in the rest of the disclosure. Such compositions, in some embodiments, are effective in treating a condition associated with polypeptide aggregation. Such compositions, in some embodiments, are effective in treating a condition associated with tau protein fibrillation. In certain aspects, the disclosed compositions further comprise a pharmaceutically acceptable excipient. In some embodiments, the excipient increases membrane permeability to peptides. In some aspects, the disclosed methods of treating or preventing a condition associated with polypeptide aggregation in a subject in need thereof comprise administering the peptidic compound described above and in the rest of the disclosure or the composition described above and in the rest of the disclosure to the subject, thereby treating or preventing the condition. In some embodiments, the condition is associated with tau protein fibrillation. In some embodiments, the agents and compositions described herein are administered intravenously, intranasally, or intramuscularly. In some embodiments, the condition comprises Alzheimer's disease. In other embodiments, the condition comprises progressive supranuclear palsy, which is shown also to be sensitive to treatment with EGCG, or chronic traumatic encephalopathy, which is structurally related to AD-tau fibrils that contain the EGCG binding cavity that is described here, or other tauopathy. In some embodiments, the subject is a human. In some aspects, the disclosed methods of diagnosing a condition associated with polypeptide aggregation in a subject in need thereof comprise administering to the subject an effective amount of one or more peptidic compound described above and in the rest of the disclosure or the composition described above and in the rest of the disclosure to the subject, thereby treating the condition; scanning the subject by a magnetic resonance imaging (MRI) spectroscopy to get an MRI scan; and diagnostically processing the MRI scan derived from magnetic resonance imaging (MRI) spectroscopy. In some embodiments, the diagnosed condition is associated with tau protein fibrillation. In some embodiments, the agents and compositions described herein for diagnosing are administered intravenously, intranasally, or intramuscularly. In some embodiments, the diagnosed condition comprises Alzheimer's disease. In other embodiments, the diagnosed condition comprises progressive supranuclear palsy, which is shown also to be sensitive to treatment with EGCG, or chronic traumatic encephalopathy, which is structurally related to AD-tau fibrils that contain the EGCG binding cavity that is described here, or other tauopathy. In some embodiments, the subject is a human. In some embodiments, the disclosed method of destabilizing a tau amyloid fibril, includes contacting the tau amyloid fibril with one or more of the agents described above and in the rest of the disclosure. Definitions As used in the description, the words “a” and “an” can mean one or more than one. As used in the claims in conjunction with the word “comprising,” the words “a” and “an” can mean one or more than one. As used in the description, “another” can mean at least a second or more. The term “treating” includes curing, relieving, or ameliorating to any extent a symptom of an illness or medical condition or inhibiting further worsening of such a symptom. For example, treating Alzheimer’s disease includes making the Alzheimer’s disease less severe or slowing its progression. The phrase “pharmaceutically-acceptable carrier” as used herein means a pharmaceutically-acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material. Each carrier must be “acceptable” in the sense of being compatible with the other ingredients of the formulation and not injurious to the subject. Some examples of materials which can serve as pharmaceutically-acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer’s solution; (19) ethyl alcohol; (20) phosphate buffer solutions; and (21) other non-toxic compatible substances employed in pharmaceutical formulations. As used herein, “peptidic compound” encompasses peptides, including, without limitation, those of up to 4, 5, 6, 7 or more amino acid residues in length, and also includes amino acid residues with D or L stereochemistry, and longer peptides and related compounds whose structure and binding capacity serve to inhibit fibril formation. “Peptidic compound” also encompasses peptidomimetic compounds. As used herein, “peptidomimetic,” also referred to as “peptide mimetic,” means any compound containing non-peptidic structural elements that is capable of mimicking the biochemical and / or biological action(s) of a natural mimicked peptide, including, for example, those designed to mimic the structure and / or binding activity (such as, for example, hydrogen bonds and hydrophobic packing interactions) of the peptides according to the methods disclosed herein. The amyloid-binding region of the mimetic can comprise amino acid residues, whether D- or L-, whether natural or non- naturally occurring, and it can also comprise non-amino acid moieties. Peptidic compounds of the invention are those with a moiety whose structure and binding capacity enables it to inhibit fibril formation generally found in neural and / or systemic disorders characterized by fibril formation, such as those involving tau protein. From an inhibitory peptidic compound according to the invention, a person of ordinary skill using molecular modeling tools can design a peptide mimetic having the biochemical structure and / or binding activity (such as, for example, hydrogen bonds and hydrophobic packing interactions) of the inhibitory peptide, that is, it binds to the steric zipper region to inhibit fibrillation, in vivo and in vitro. As used herein, “aggregation” means the collection and association of peptide moieties, whether the resulting structure is regular or irregular, repeating or non- repeating, stable or unstable or with ordered or disordered native states. Such association can occur through intermolecular interactions, ionic bonds, hydrophobic interactions, hydrogen bonds, van der Waals forces, i.e., “London dispersion forces,” and dipole-dipole bonds, or any force or substance that can result in the collection or association together of two or more peptides or peptide regions. As used herein, “aggregation” encompasses, for example, fibrillation, assembly, or the formation of fibrils. “Aggregation” also encompasses the formation of amyloid fibrils. As used herein, a “target protein” or “target polypeptide” means any peptide structure that has a tendency to form fibrils, for example amyloid fibrils. Examples of target proteins include, without limitation, amyloid beta, tau, α-synuclein, TDP-43, TMEM106B, hnRNPA1, hnRNPA2, FUS, islet amyloid polypeptide (IAPP), beta-2-microglobulin, semen-derived enhancer of viral infection (SEVI) immunoglobulin light chains, Huntington protein, PrP prion protein and lysozyme. As used herein, “aggregation” encompasses “fibrillation.” As used herein, “inhibiting,” in the context of fibril formation, can include preventing, reducing, disrupting or slowing the rate of increase of fibril formation, in vitro or in vivo, in a cell-free system, a cell culture, in tissue, or in an organism, including an animal such as a human or other mammal. As used herein, “destabilizing,” in the context of fibril disaggregation, can include disaggregating, disassembling fibril, or reducing the fibril content, in vitro or in vivo, in a cell-free system, a cell culture, in tissue, or in an organism, including an animal such as a human or other mammal. “Polypeptide aggregation-associated condition,” or “condition associated with polypeptide aggregation,” as used herein, means conditions characterized by the aggregation of polypeptides of a kind, or to a degree, that is not commonly observed in healthy subjects. Examples of such conditions include, for example, Alzheimer's disease; Parkinson's disease (α-synuclein amyloidosis); amyotrophic lateral sclerosis (commonly known as Lou Gehrig's disease); type II diabetes (islet amyloid polypeptide (IAPP) amyloidosis); lysozyme amyloidosis; disorders associated with amyloid formation involving transthyretin fibrillation, such as, for example, familial and senile amyloidosis; prion diseases (CVJ, vCJD, GSS); cardiac amyloidosis; HIV sexual transmission associated with the SEVI form of prostate activating protein of semen and antibody light chain amyloidosis affecting kidney function. As used herein, “target polypeptide” encompasses, for example, whole, native polypeptides with a feature that favors aggregation, such as a zipper-forming sequence; partial polypeptides that retain the aggregation-favoring feature; or mimetics that include the aggregation-favoring feature but that also include non- peptide structural elements. The term “subject” refers to a mammal, including, but not limited to, a human or non-human mammal, such as a bovine, equine, canine, ovine, or feline. Agents and Compositions In some aspects, the present disclosure provides agents that are effective in inhibiting tau aggregation and / or disaggregating tau amyloid fibrils, and thus can be used to treat a tauopathy. The agents, in various embodiments, can destabilize a tau amyloid fibril when in contact with the tau amyloid fibril. In some embodiments, the agents are permeable across the blood-brain barrier. Such disclosed agents include a) a binding and / or disaggregating moiety that adheres to a target polypeptide in its amyloid fibril form, and proceeds to inhibit the target protein and / or disaggregate the fibril form, and b) a nanomass moiety that promotes transfer of the agent to a site of the target polypeptide. The nanomass moiety includes a magnetic nanoparticle (MNP). The binding and / or disaggregating moiety is a peptidic compound that inhibits aggregation of the target polypeptide and / or disassembles a target polypeptide aggregate, and the nanomass moiety includes a magnetic nanoparticle, wherein the target polypeptide includes a protein sequence within an amyloid fibril. In some embodiments, the agent can be D-TLKIVWC (SEQ ID NO: 2) (DP) liganded magnetic nanoparticles (MNP), MNPs-DP. In some other embodiments, the agent can be D-TLKIVWC (SEQ ID NO: 2) (DP) liganded iron oxide magnetic nanoparticles (IONP), a structure of which is depicted in FIG.1A. FIG.1B shows that, based on the present disclosure, the carboxylic acid iron oxide magnetic nanoparticles were reacted with 2-Maleimidoethylamine hydrochloride to produce maleimide-functionalized iron oxide nanoparticles, which were further conjugated with D-TLKIVWC (SEQ ID NO: 2) to obtain the D-TLKIVWC (SEQ ID NO: 2) - MNPs through the thiol-maleimide Michael addition click reaction. In some embodiments, the magnetic nanoparticle is an iron oxide nanoparticle (IONP). An IONP can further be coated through suitable means, such as those described in Arami H. et al., In vivo delivery, pharmacokinetics, biodistribution and toxicity of iron oxide nanoparticles, Chem Soc Rev.44(23): 8576–8607 (2015). As an example, the coating may include polyethylene glycol (PEG), dextran (e.g., dextran- 20kDa, dextran-40kDa, carboxy dextran, or cross-linked dextran-20kDa), starch, chitosan, lipid, citrate, polyaniline, meso-2,3-dimercaptosuccinic acid, poly(maleic anhydride-alt-1-octadecene), polyacrylamide, phosphonate, or silica. Table N provides some examples of iron oxide nanoparticles. Table N: Examples of iron oxide nanoparticles (a type of carrier) Polyglucose sorbitol carboxymethylether-coated iron oxide (ferumoxytol) (e.g., ferumoxytol AMI-7228) The present disclosure also provides compositions for treating a tauopathy. The compositions, in various embodiments, include the agents described above and in the rest of this disclosure. Such compositions can be effective in treating tauopathies, such as Alzheimer's disease. The composition may comprise a carrier (e.g., a pharmaceutically-acceptable carrier, for any of the disclosed embodiments). The pharmaceutical compositions disclosed herein may be delivered by any suitable route of administration (e.g., oral, intravenous, intranasal, intramuscular), and can be supplied in various forms (e.g., powders, ointments, drops, liquids, gels, tablets, capsules, pills, or creams). Methods of Destabilizing a Tau Amyloid Fibril and of Treating a Tauopathy In some aspects, the present disclosure provides methods for treating or preventing a condition associated with polypeptide aggregation, for example, a tauopathy, wherein the condition is associated with tau protein fibrillation, in a subject in need thereof. Such methods include administering to the subject an effective amount of a composition disclosed in the “Agents and Compositions” section as well as in the rest of this disclosure. The administration of the compositions can be oral, intravenous, intranasal, or intramuscular. The treated tauopathy, in some embodiments, includes Alzheimer's disease, progressive supranuclear palsy, chronic traumatic encephalopathy, and / or other tauopathy. The selected dosage level, as can be determined by a medical practitioner, will depend upon a variety of factors including the activity of the particular agent employed, the route of administration, the time of administration, the rate of excretion or metabolism of the particular compound being employed, the duration of the treatment, other drugs, compounds and / or materials used in combination with the particular compound employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts. The present disclosure also provides methods for destabilizing a tau amyloid fibril. Such methods include contacting the tau amyloid fibril with an agent disclosed in the “Agents and Compositions” section as well as the rest of this disclosure. The tau amyloid fibril may include a paired helical filament, and the used agent can dis- aggregate that paired helical filament, for example by disrupting ion pairing of lysine at position 340 of tau with respect to SEQ ID NO: 1 by forming at least one hydrogen bond with said lysine. MAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSE EPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSL EDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRI PAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAV VRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLS NVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSE KLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVV SGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGL (SEQ ID NO: 1) EXAMPLES EXAMPLE 1: SYNTHESIS OF D-TLKIVWC (SEQ ID NO: 2) LIGANDED IRON OXIDE MAGNETIC NANOPARTICLES (D-TLKIVWC (SEQ ID NO: 2) -MNPS) Experiments with DP and MNPs-DP in vitro Recombinant Tau protein expression and purification Recombinant Tau K18+ (residues Gln244-Glu380 of 4R tau) was expressed in a pNG2 vector in BL21-Gold E. coli cells grown in LB to an A600 = 0.8. Cells were induced with 0.5 mM isopropyl 1-thio-β-D-galactopyranoside for 3 h at 37 °C and lysed by sonication in 20 mM MES buffer (pH 6.8) with 1 mM ethylenediaminetetraacetic acid (EDTA), 1 mM MgCl2, 1 mM DTT, and HALT protease inhibitor before the addition of NaCl (500 mM final concentration). Lysate was boiled for 20 min and then clarified by centrifugation at 15,000 rpm for 15 min and dialyzed to 20 mM MES buffer (pH 6.8) with 50 mM NaCl and 5 mM DTT. Dialyzed lysate was purified on a 5-ml HighTrap SP ion exchange column and eluted over a gradient of NaCl from 50 to 550 mM. Protein was polished on a HiLoad 16 / 600 Superdex 75 pg column in 10 mM Tris (pH 7.6) with 100 mM NaCl and 1 mM DTT and concentrated to 20-60 mg / ml by ultrafiltration using a 3-kDa cutoff. The synthesis of D-TLKIVWC (SEQ ID NO: 2) liganded iron oxide magnetic nanoparticles involves two steps as shown in FIG. 1B. First, the carboxylic acid iron oxide magnetic nanoparticles (MNPs, Creative Diagnostics, WHM-G062) were reacted with 2-Maleimidoethylamine hydrochloride to gain the maleimide-functionalized iron oxide nanoparticles, which were further conjugated with D-TLKIVWC (SEQ ID NO: 2) to obtain the D-TLKIVWC (SEQ ID NO: 2) -MNPs through the thiol-maleimide Michael addition click reaction. Briefly, 1 mg of N-hydroxysulfosuccinimide (Sulfo- NHS) and 1.5 mg of N-ethyl-N′-(3-(dimethylamino)propyl)carbodiimide (EDC) were dissolved in 50 uL activation buffer (0.1 M MES, 0.5 M NaCl, pH 6.0) separately before they were added to the 200 uL 5 mg / ml MNPs with 100 µl activation buffer and continuously shaken at room temperature for 15 minutes. Next, 2 mg of 2- Maleimidoethylamine hydrochloride that dissolved in 500 µl 20X PBS was added to the above solution and shaken at room temperature for another 2 hours. After that, the solution was kept in a magnetic separator in 4℃. After three rounds of magnetic separation and washing, the supernatant was removed and the nanoparticles were resuspended in 1 mL 1X Tris buffer (pH 7.04) by sonication for several hours. In the second step, 4 mg of D-TLKIVWC (SEQ ID NO: 2) was dissolved in 1X Tris buffer (pH 7.04) and then added to the above magnetic nanoparticles solution. The mixed solution was kept rotated at room temperature for 1 hour before transfer to a magnetic separator. After three rounds of magnetic separation and washing, the D-TLKIVWC (SEQ ID NO: 2) -MNPs was finally resuspended in 1X PBS and kept at 4℃ before usage. The morphology of the nanoparticles was observed by FEI Tecnai T12 Quick room temperature TEM at 120 kV. EXAMPLE 2 : THIOFLAVIN T (THT) INHIBITION ASSAY A frozen aliquot of the purified recombinant tau-K18+ was thawed on ice and as diluted into PBS (pH 7.4) to a final concentration of 20 micromolar (μM). In vitro aggregation was initiated by incubating 150 microliter (μl), 20 μM tau-K18+ monomer in presence of 40 mM Thioflavin T (ThT), 0.225 mg / ml heparin and 1 mM dithiothreitol in a black Nunc 96-well optical bottom plates (Thermo Scientific). To test the effect of D-TLKIVWC (SEQ ID NO: 2) -MNPs and D-TLKIVWC (SEQ ID NO: 2) on inhibiting tau-K18+ aggregation, tau K18+ monomer was incubated in the presence of different concentrations of D-TLKIVWC (SEQ ID NO: 2) -MNPs (0.005, 0.01, 0.02 mg / ml), D-TLKIVWC (SEQ ID NO: 2) (5, 10, 20, 50, 100 μM), or D-TLKIVW (SEQ ID NO: 13) (5, 10, 20, 50, 100 μM). Kinetic fluorescence data were collected in a microplate reader (FLUOstar Omega, BMG Labtech) at 37˚C with double orbital shaking at 700 rpm. Fluorescence measurements were recorded every 10 mins with excitation and emission wavelengths of 444 and 482 nm, All samples were added in triplicate and experiments were repeated at least twice. FIG.2 is a plot of fluorescence intensity of the amyloid-sensitive dye Thioflavin T (ThT) as a function of time showing that MNPs-DP (i.e. D-TLKIVWC (SEQ ID NO: 2) -MNPs) inhibit fibril formation of tau K18+. Tau K18+ is a recombinant construct of tau comprising residues 244-380, which cover the ordered portion of tau fibrils extracted from AD brains, the negative control (black curve) shows fibril formation of un-inhibited tau K18+. EXAMPLE 3: THIOFLAVIN T DISAGGREGATION ASSAY 20 μM tau-K18+ monomer was grown in presence of 40 mM Thioflavin T (ThT), 0.225 mg / ml heparin and 1 mM dithiothreitol overnight to form the fibrils. The tested D-TLKIVWC (SEQ ID NO: 2) -MNPs, naked MNPs, D-TLKIVWC (SEQ ID NO: 2) , D-TLKIVW (SEQ ID NO: 13) was added separately to designated wells, and the ThT assay was further continued. Kinetic fluorescence data were collected in a microplate reader (FLUOstar Omega, BMG Labtech) at 37˚C with double orbital shaking at 700 rpm. Fluorescence measurements were recorded every 10 mins with excitation and emission wavelengths of 444 and 482 nm, All samples were added in triplicate and experiments were repeated at least twice. FIG.3A to 3D present a series of electron micrographs showing that the MNPs- DP can inhibit the aggregation of tau K18+ fibrils and is dose-dependent. FIG. 3A is when tau monomers are incubated alone in vitro. FIG.3B, FIG.3C, and FIG.3D show that the length of the obtained tau fibrils gradually decreases with the increase of MNPs- DP. FIG. 3D shows that a lot of spherical structures are observed at the high concentration of MNPs-DP. Transmission electron microscopy 6 μL of sample was applied to a glow discharged carbon coated electron microscopy grid (CF150-Cu, Electron Microscopy Sciences) for 5 minutes. Then grids were stained with 2% uranyl acetate for 2 minutes. Samples were visualized using a FEI Tecnai T12 Quick room temperature transmission electron microscope using an acceleration voltage of 120 kV equipped with a Gatan 2,048 x 2,048 CCD camera. Cell viability of Tau K18+ aggregates Tau K18+ aggregates were produced by incubation of tau K18+ (20 μM) in the absence or presence of 5, 10, 20, 50, 100 uM D-TLKIVWC (SEQ ID NO: 2) or D-TLKIVW (SEQ ID NO: 13) for 48 h in PBS. PBS without any protein was used as controls. N2a cells were cultured in Minimum Essential Medium (MEM) supplemented with 10% (v / v) fetal bovine serum, 1% antibiotic-antimycotic, and 1% Glutamax in a 5% CO2 humidified environment at 37 °C. Cells were plated at a density of 10,000 cells / well on 96-well plates in 90 μL of fresh medium. After 24 h, 10 μL of the above Tau K18+ aggregates were added, and the cells were incubated for another 24 h at 37 °C. Cytotoxicity was measured utilizing the 3-4,5- dimethylthiazolyl-2,5-diphenyltetrazolium bromide (MTT) assay.10 μl of the stock MTT reagent (5 mg / ml) was added to each well. After 3 h of conversion into the formazan product, DMSO was added to dissolve the purple crystals left in the dark for 10 min before the measurement of absorbance at 570 nm with 700 nm as a subtracted reference wavelength. To further investigate the cytotoxicity of D-TLKIVWC (SEQ ID NO: 2) and D-TLKIVW (SEQ ID NO: 13) , various concentrations of D- TLKIVWC (SEQ ID NO: 2) and D-TLKIVW (SEQ ID NO: 13) (2, 5, 10, 20, 50, 100, 200 μM) were dispensed into the N2a cells, and further incubated for 24 h at 37°C and in 5% CO2 incubator. Cytotoxicity was measured using a MTT assay. Cell toxicity of Tau K18+ fibril disaggregation species Tau K18+ fibril disaggregation species were produced by incubating Tau K18+ fibrils with 2.5, 5, 10, 20, 50, 100, 200 uM D-TLKIVWC (SEQ ID NO: 2) or D-TLKIVW (SEQ ID NO: 13) for 24 h. N2a cells were cultured in MEM supplemented with 10% (v / v) fetal bovine serum, 1% antibiotic-antimycotic, and 1% Glutamax in a 5% CO2 humidified environment at 37 °C. Cells were plated at a density of 10,000 cells / well on 96-well plates in 90 μL of fresh medium. After 24 h, 10 μL of Tau K18+ fibril disaggregation species were added and the cells were incubated for another 24 h at 37 °C. Cytotoxicity was measured utilizing MTT assay.10 μl of the stock MTT reagent (5 mg / ml) was added to each well. After 3 h of conversion into the formazan product, DMSO was added to dissolve the purple crystals left in the dark for 1 h before the measurement of absorbance at 570 nm with 700 nm as a subtracted reference wavelength. Experiments on Alzheimer's brain extracted tau fibrils. Preparation of crude and purified AD brain tau fibrils Tissue sections of 0.2-0.3 g were excised on a block of dry ice and manually homogenized in a 15-ml disposable tube in 1.5 ml of sucrose buffer with 1mM EGTA and 5mM EDTA. Samples were then aliquoted to PCR tubes and sonicated in a cuphorn bath for 120 min under 30% power at 4 °C in a recirculating ice water bath to obtain the crude AD brain tau fibrils. For purification of tau fibrils from AD brain tissue, the crude AD brain tau samples were further heated for 20 min in thermal cycler (1st, 90℃ 20 min, 2nd, 22℃, forever) and centrifuged at 20,100 x g for 30 min. The supernatant was collected and then spined at 90K for 30m in Airfuge. Finally, the pellet was the purified AD brain-derived tau fibrils and resuspended in 20 ul 20 mM Tris buffer with 100 mM NaCl and stored at 4 ℃. Crude AD brain tau fibril seeding in tau biosensor cell line HEK293 cell lines stably expressing tau-K18-eYFP were engineered by Marc Diamond’s laboratory at the University of Texas Southwestern Medical Center and used without further characterization or authentication. Cells were maintained in Dulbecco’s modified Eagle’s medium supplemented with 10% (v / v) fetal bovine serum, 1% antibiotic-antimycotic, and 1% Glutamax at 37 °C, 5% CO2in a humidified incubator. Crude AD brain tau fibrils were incubated with D-TLKIVWC (SEQ ID NO: 2) -MNPs (0.005, 0.01, 0.02 mg / ml), D-TLKIVWC (SEQ ID NO: 2) (5, 10, 20, 50, 75, 100 μM) or D-TLKIVW (SEQ ID NO: 13) (5, 10, 20, 50, 75, 100 μM) overnight and sonicated in a cup horn water bath for 3 min. Then these inhibitors-treated tau seeds were mixed with 1 volume of Lipofectamine 3000 prepared by diluting 1μL of Lipofectamine in 19 μL OptiMEM. After 20 min, 10 μL of fibrils were added to 90 μL tau biosensor cells. The number of seeded aggregates was determined by imaging the entire well of a 96-well plate in triplicate using a Celigo image cytometer (Nexcelom) in the YFP channel. Aggregates were counted using ImageJ by subtracting the background fluorescence from unseeded cells and then counting the number of peaks with fluorescence above background using the built-in particle analyzer. The number of aggregates was normalized to the confluence of each well, and dose-response plots were generated by calculating the average and S.D. values from triplicate measurements. For high-quality images, cells were photographed on a ZEISS Axio Observer D1 fluorescence microscope using the YFP fluorescence channel. Disaggregation of purified AD brain-derived tau fibrils Purified AD brain tau fibrils were incubated with D-TLKIVWC (SEQ ID NO: 2) -MNPs (0.05 mg / ml), MNPs (0.05 mg / ml), D-TLKIVWC (SEQ ID NO: 2) (500 μM) and D-TLKIVW (SEQ ID NO: 13) (500 μM) at 37 ℃ for 48 h, respectively.6 μL of sample was applied to a glow discharged carbon coated electron microscopy grid (CF150-Cu, Electron Microscopy Sciences) for 5 minutes. Then grids were stained with 2% uranyl acetate for 2 minutes. Samples were visualized using a FEI Tecnai T12 Quick room temperature transmission electron microscope using an acceleration voltage of 120 kV equipped with a Gatan 2,048 x 2,048 CCD camera. The fibrils in each image was counted. Dot blot Assay Purified AD brain tau fibrils were incubated with D-TLKIVWC (SEQ ID NO: 2) -MNPs (0.05 mg / ml), MNPs (0.05 mg / ml), D-TLKIVWC (SEQ ID NO: 2) (500 μM) and D-TLKIVW (SEQ ID NO: 13) (500 μM) at 37 ℃ for 48 h, respectively.15 ul of samples were added on nitrocellulose membrane (0.2 µm, Bio-Rad, Hercules, CA). The membrane was blocked by 5% (w / v) nonfat dry milk in TBS-T (T = 0.1% (v / v) Tween-20) at room temperature for 1 hr. After blocking, the membrane was incubated with Anti-Amyloid Fibrils OC Antibody (1:1000, AB2286MI) in 5% (w / v) milk in TBS-T at room temperature for 1.5 h. Then, the membrane was washed in TBS-T for three times and incubated with Goat Anti-Rabbit IgG (H+L) HRP (A27036) diluted 1:5000 in TBS-T for 1 hr at room temperature. The membrane was washed three more times and the signal was developed with PierceTMECL western blotting substrate (170-5061, BioRad). Experiments on mice Animals P301S transgenic mice (Prnp-MAPT*P301S PS19Vle / J, Jackson Laboratory, Bar Harbor, ME) express the P301S mutant human microtubule-associated protein tau (MAPT) under the control of the mouse prion protein promoter. Animals were housed in groups of up to five in individually ventilated cages under standard conditions (22℃, 12 h light-dark cycle) receiving food and water ad libitum. All animal experiments were performed in accordance with the National Institutes of Health regulations and approved by the committee of animal use for research at the University of California, Los Angeles. Treatment We seeded 15 six-month-old, female PS19 mice with recombinant K18 tau and divided those 15 mice into three groups. Each group was intravenously administered with PBS, unliganded MNPs, or D-TLKIVWC (SEQ ID NO: 2) -MNPs every week for 10 weeks. The weight of mice were recorded weekly. Treatment with unliganded MNPs or D-TLKIVWC (SEQ ID NO: 2) -MNPs was always in combination with intranasal administration of mannitol. Four wild-type, age-matched C57BL / 6 female mice were stereotactically injection with PBS to serve as controls. Behavioral tests All the animals were handled for at least 3-4 consecutive days before testing. They were tested in random order and the experimenter conducting the tests was unaware of the genotype / group. Barnes Maze The maze consisted of a circular platform with 20 holes around the periphery with an escape box attached to the bottom of one of the holes and shallow boxes attached to the bottom of the other holes. Bright light and white noise were used to motivate mice to find and enter the escape box. Visual extra-maze cues were present on 3 walls of the room. For all trials, mice were placed individually in a cylindrical start chamber in the center of the maze for 30 s, which was then lifted to start the test. During an adaptation period, mice were guided to the escape tunnel and allowed to stay there for 30 s. During a spatial acquisition period, a total of 12 acquisition trials (3 trials per day with an inter-trial interval of 15 min) were performed; mice were allowed to explore the maze freely for 2 min. Each trial ended when the mouse entered the escape tunnel or after 2 min had elapsed. Mice that did not find the tunnel were guided to it. All mice were allowed to remain in the tunnel for 30 s. During the probe trial conducted 1 day after the last training trial, the escape tunnel was replaced by a shallow box and mice were allowed to explore the maze for 90 s. Animals’ performances were monitored using Any-Maze™ Video Tracking System (Stoelting Co., Wood Dale, IL), which provided data for the acquisition parameter (latency to find the platform) and the probe trial parameters (latency to find the platform, number of entries in the target platform zone of the platform, distance and time in quadrants). Rotarod test Motor coordination and balance were tested using an accelerating rotarod with an initial speed of 1 RPM and a maximum speed of 60 RPM. The drum was slowly accelerated by 0.5 rotations per minute (RPM) per 2 s. The mice were subjected to training trials twice a day for 3 consecutive days. As the subjects fall down or rotate with the cylinder, the trial was finished and write down the time and RPMs. Statistical analysis Graphs are expressed as means-standard error of the mean (SEM) and were analyzed using SPSS 19.0 statistical analysis software (SPSS, Chicago, IL, USA). One-way analysis of variance (ANOVA) followed by a LSD post-test were used to analyze difference among multiple groups. Statistical differences for all tests were considered significant at the *p < 0.05, **p < 0.01, ***p < 0.001 levels. EXAMPLE 4: PEPTIDES D-TLKIVWX (SEQ ID NO: 14), WHERE X COMPRISES AN AMINO ACID RESIDUE SELECTED FROM: C,A,S,D,I,V,R,K,E,P,T DISAGGREGATE TAU FIBRILS As noted above, we have discovered that the 7-residue D-TLKIVWC (SEQ ID NO: 2) peptide and its covalent complex with iron oxide magnetic nanoparticles (D- TLKIVWC (SEQ ID NO: 2) -MNP) can disassemble (disaggregate) tau fibrils extracted from autopsied AD brains, and to some extent reverses neurological deficits of mice harboring mutant tau that produces these neurological deficits. We have further discovered that peptides that replace the terminal cysteine (C) in TLKIVWC (SEQ ID NO: 2) with residues including alanine (A) or serine (S) also possess an ability to disaggregate. In this context, embodiments of the invention include peptides that substitute / replace the terminal cysteine in TLKIVWC with any of isoleucine (I), valine (V), arginine (R), lysine (K), glutamic acid (E), threonine (T) also can disaggregate tau fibrils extracted from autopsied AD brains. The dot blot results in Figure 25 and Figure 26 show that the D-TLKIVWX (SEQ ID NO: 14) (X=C, A, S, I, V, R, K, E, T) reduce the amyloid fibril content of AD brain tau fibrils, demonstrating that D-TLKIVWX (SEQ ID NO: 14) (X=C, A, S, I, V, R, K, E, T) disaggregate AD Tau fibrils, which is further confirmed by the EM characterization (Figure 27). Here D-TLKIVWX (SEQ ID NO: 14) (X=C,A,S,D,I,V,R,K,E,P,T) are abbreviated as DP-X (X=C,A,S,D,I,V,R,K,E,P,T). METHODS Dot blot assay Purified AD brain tau fibrils were incubated with H2O, 500 μM D-TLKIVW (SEQ ID NO: 13) (S-DP) and D-TLKIVWX (SEQ ID NO: 14) (X=C,A,S,D,I,V,R,K,E,P,T) at 37 ℃ for 48 h, respectively.15 ul of samples were added on nitrocellulose membrane (0.2 µm, Bio-Rad, Hercules, CA). The membrane was blocked by 5% (w / v) nonfat dry milk in TBS-T (T = 0.1% (v / v) Tween-20) at room temperature for 1 hr. After blocking, the membrane was incubated with Anti- Amyloid Fibrils OC Antibody (1:1000, AB2286MI) in 5% (w / v) milk in TBS-T at 4 ℃ overnight. Then, the membrane was washed in TBS-T for three times and incubated with Goat Anti-Rabbit IgG (H+L) HRP (A27036) diluted 1:5000 in TBS-T for 1 hr at room temperature. The membrane was washed three more times and the signal was developed with PierceTMECL western blotting substrate (170-5061, BioRad). Electron Microscopy Characterization The specimen preparation and data collection are same as indicated above. Results Figure 25 shows dot blot data from AD brain tau fibrils after incubation with H2O, 500 μM D-TLKIVW (SEQ ID NO: 13) (S-DP) and D-TLKIVWX (SEQ ID NO: 14) (X=C,A,S,D,I,V,R,K,E,P,T), respectively. The primary antibody is Anti- Amyloid Fibrils OC Antibody (1:1000). Figure 26 shows quantification of chemiluminescence data from dot blot assay in Fig.25 calculated using FIJI.16 bit using int density. Figure 27 shows electron microscopy images of AD tau fibrils after incubation with H2O, 500 μM D-TLKIVW (SEQ ID NO: 13) (S-DP) and D- TLKIVWX (SEQ ID NO: 14) (X=C,A,S,D,I,V,R,K,E,P,T) for 48 h. EXAMPLE 5: D-TLKIVWX (SEQ ID NO: 14) SHOWS SPECIFICITY IN DISASSEMBLING TAU FIBRILS D-TLKIVWX (SEQ ID NO: 14) shows a degree of specificity in disassembling tau fibrils (from PSP, CTE, CBD…). In addition to tau fibrils extracted from AD brains (AD-tau), D-TLKIVWI (SEQ ID NO: 15) disaggregates tau fibrils extracted from progressive supranuclear palsy (PSP) brains but has no effect on α-syn fibrils from multiple system atrophy (MSA) brains (Fig.28a,b). Similarly, D-TLKIVWX (SEQ ID NO: 14) effectively disaggregates recombinant tau K18+ fibrils but does not affect recombinant α-syn fibrils or wild-type hnRNPA2 fibrils (Fig.28c-f). In particular, as shown in Fig. 28, D-TLKIVWX (SEQ ID NO: 14) shows specificity in disassembling tau fibrils. a, Representative TEM images of tau fibrils extracted from progressive supranuclear palsy brain (PSP tau fibrils) alone and after incubation with 500 μM D-TLKIVWI (SEQ ID NO: 15) for 48 hours. b, Representative TEM images of α-syn fibrils extracted from multiple system atrophy brain (MSA α-syn fibrils) alone and after incubation with 500 μM D-TLKIVWI (SEQ ID NO: 15) for 48 hours. c, Representative TEM images of recombinant α-syn fibrils alone and after incubation with 50 μM D-TLKIVWI (SEQ ID NO: 15) for 24 hours. d, Representative TEM images of wild-type (WT) hnRNPA2 low complexity domain (LCD) fibrils alone and after incubation with 100 μM D-TLKIVWI (SEQ ID NO: 15) for 55 hours. e, ThT assay of 25 μM α-syn fibrils incubated with 50 μM fresh D-TLKIVW (SEQ ID NO: 13) or D-TLKIVWX (SEQ ID NO: 14) (X = C, A, S, D, I, V, R, E, P, T) at 95 h time-point. f, ThT assay of 10 μM WT hnRNPA2 low complexity domain (LCD) fibrils incubated with 100 μM fresh D-TLKIVW (SEQ ID NO: 13) or D-TLKIVWX (SEQ ID NO: 14) (X = C, A, S, D, I, V, R, E, P, T) at 15 h time-point. Scale bars, 0.2 µm. D-TLKIVWX (SEQ ID NO: 14) peptides form right-handed mock-amyloid fibrils D-TLKIVWX (SEQ ID NO: 14) can form right-handed D-TLKIVWX (SEQ ID NO: 14) (X = I, S and R) fibrils (Fig.29a). Under cryoEM, the D-TLKIVWX (SEQ ID NO: 14) (X = I, S and R) fibrils are each composed of different numbers of protofilaments and these protofilaments associate in different patterns, but all the protofilaments share the same underlying structural motif known as a "steric zipper", a pair of β-sheets mated together by an interface of snugly fitting sidechains (Fig.29b-d). In addition, the steric zippers formed by D-TLKIVWX (SEQ ID NO: 14) (X = I, S and R) all share the same symmetry pattern in which antiparallel β-sheets mate together by interfacing sidechains of Leu2, Ile4, and Trp6 (an example of “class 5” symmetry). As a result, the helical rise of D-TLKIVWX (SEQ ID NO: 14) (X = I, S and R) amyloid- like fibrils is 9.56 Å, twice that of the 4.80 Å spacing that is common among pathogenic amyloid fibrils. In particular, as shown in Fig. 29, D-TLKIVWX (SEQ ID NO: 14) (X = I, S, R) peptides form right-handed helical fibrils with conserved steric zipper motifs. a, Representative atomic force microscopy (AFM) image of D-TLKIVWI (SEQ ID NO: 15) fibrils. b-d, Views down the fibril axes (upper row) and perpendicular to the fibril axes (lower row) of the amyloid-like fibrils formed by (b) D-TLKIVWI (SEQ ID NO: 15), (c) D-TLKIVWS (SEQ ID NO: 10) , (d) D-TLKIVWR (SEQ ID NO: 16) , as determined by cryo-EM. The conserved steric zipper motifs are represented by grey dotted ellipses. D-TLKIVWX (SEQ ID NO: 14) adopt a left-handed twist when templated in complex with AD-tau Helical reconstructions of the AD-tau complexed with each of the three D- peptides revealed the paired helical filament (PHF) tau polymorph with its usual left- handed twist (Fig. 30a-c), and the atoms modeled into the PHF density showed no significant structural deviations from the negative control. However, the cryo-EM map of PHF complexed with D-TLKIVWX (SEQ ID NO: 14) (X =I, S and R) revealed residual density near Val313-Thr319 (highlighted yellow in Fig. 30a) of PHF, which was absent from our control (Fig.30d). The shape of the residual density resembles one steric zipper unit of D-TLKIVWX (SEQ ID NO: 14) fibrils. Refinement of the 3D reconstruction of D-TLKIVWX (SEQ ID NO: 14) (X =I, S and R) complexed with Tau PHF achieved overall resolutions of 3.1 Å, 3.1 Å and 3.5 Å, In particular, as shown in Fig. 30, D-TLKIVWX (SEQ ID NO: 14) mock- amyloid fibrils form along left-handed AD-tau and drive the fragmentation of AD-tau. a-c, Cryo-EM density, and atomic models of a cross section of PHF fibrils complexed with (a) D-TLKIVWI (SEQ ID NO: 15), (b) D-TLKIVWS (SEQ ID NO: 10) , and (c) D-TLKIVWR (SEQ ID NO: 16) , with views down the fibril axes (upper row) and from the side of the fibril axes (lower row). Details of the PHF structures are evident in sharpened, high-resolution density maps of the PHFs (dark salmon). The D-peptides are visible in unsharpened, low-pass filtered density (7 Å) colored blue (D-TLKIVWI (SEQ ID NO: 15)), marine (D-TLKIVWS (SEQ ID NO: 10) ), and green (D-TLKIVWR (SEQ ID NO: 16) ). The corresponding low-pass filtered density of the PHF is shown in light salmon. Residues Val309-Thr319 are highlighted in yellow in panel a. d, Cryo- EM density, and atomic models of a cross section of PHF fibrils (AD-tau control). Release of strain in the D-TLKIVWX (SEQ ID NO: 14) protofilament drives the fragmentation of AD-tau High-speed atomic force microscopy (HS-AFM) provides direct visualization of the disaggregation. Fragmentation of individual AD-Tau into species too small to detect by HS-AFM takes only about ten minutes (Fig.31), but does not commence until several hours of incubation with the peptide. This lag is the time required for AD-Tau to seed the formation of D-TLKIVWI (SEQ ID NO: 15) mock-amyloid fibrils, forming a complex such as shown in Fig. 30. Of special interest, fragmentation does not occur at fibril ends but instead occurs along periodic grooves (indicated by red arrows), producing initial fragments approximately 25 nm in length (estimated by the length of blue arrows in Fig. 31). These fragments subsequently destabilize further, losing their fibrillar structure, and finally transition to an amorphous state in solution, as evidenced by the gradual decrease of the height of fibrils under HS-AFM. Notably, the fibril axis of AD-tau (marked by blue arrows in Fig. 31) at the broken ends exhibit a consistent sense of conversion that reflect the left-to-right twist of the D-TLKIVWX (SEQ ID NO: 14) mock amyloid fibril, like a torque-like effect propagating along the AD-tau to drive its fragmentation. In particular, as shown in Fig. 31, fragmentation of AD-tau after six hours of incubation with 500 μM D-TLKIVWI (SEQ ID NO: 15) was observed using high-speed atomic force microscopy (HS-AFM). The time stamps shown represents the observation time for a random region of the sample. The vulnerable grooves of AD-tau are highlighted by red arrows. Fragments of AD-tau are traced by blue arrows each of length 25 nm. Strain-relief mechanism Without being bound by a particular theory or mechanism of action, we propose the strain-relief mechanism of amyloid fibril disassembly. First, monomers or small oligomers of D-TLKIVWX (SEQ ID NO: 14) bind and nucleate on the surface of AD- tau (Fig. 32a,b). Owing to its mock-amyloid nature, D-TLKIVWX (SEQ ID NO: 14) protofilaments extend from the nuclei, but are constrained to adopt the left-handed helical twist of AD-tau PHFs, as the cryo-trapped structure of Figure 31a (Fig. 32c). Additionally, the constraint of contacting a region of AD-tau that is far from its helical axis, stretches backbone hydrogen bonds between neighboring D-TLKIVWX (SEQ ID NO: 14) molecules (by 0.2 Å) relative to a relaxed state. Since D-TLKIVWX (SEQ ID NO: 14) fibrils have an intrinsic right-handed twist, and a smaller radius, a strain develops and increases as the left-twisting D-TLKIVWX (SEQ ID NO: 14) mock- amyloid fibrils grow along AD-tau (Fig. 32d). This strain is relieved as the D- TLKIVWX (SEQ ID NO: 14) protofilament transiting its twist from a left- to right- handed helix (and shortening its hydrogen bonds), which induces a torque-like effect, breaking the local hydrogen bonding between tau molecules and drives the fragmentation of AD-tau (Fig. 32e). The eventual disassembly products are not tau monomers, but segments of complexes of tau and D-TLKIVWX (SEQ ID NO: 14) (Fig.32f). In particular, Fig.32 shows a Proposed strain-relief mechanism of disassembly of AD-tau PHF by D-TLKIVWX (SEQ ID NO: 14) peptides. a, Peptide D-TLKIVWX (SEQ ID NO: 14) (blue) is added to left-twisted AD-Tau (red). b, Nucleation of D- TLKIVWX (SEQ ID NO: 14) protofilaments on the surface of AD-tau, where they are constrained to follow the left-twisted conformation of AD-Tau, rather than their natural right-twisted structure. c, Growing segments of the D-TLKIVWX (SEQ ID NO: 14) protofilaments bound to AD-Tau stabilize the complex. d, Fully formed fibrils of left- twisted D-TLKIVWX (SEQ ID NO: 14) experience significant tortional strain (yellow) and strain energy has reached the level of the affinity of adjacent layers of AD-Tau. e, The strain in left-twisted D-TLKIVWX (SEQ ID NO: 14) fibrils is relieved by breaks in both peptide and AD-Tau. f, Fragments of AD-Tau remain bound to fragments of D- TLKIVWX (SEQ ID NO: 14). In addition, L-TLKIVWX (SEQ ID NO: 21) (X = C, I, S, R) all display inferior efficacy in disassembling AD-tau compared to their enantiomers D- TLKIVWX (SEQ ID NO: 14) (Fig.33a,b), despite similar fibril forming ability (Fig. 33c). This is because L-peptide principally possesses a left-handed twist, the same as the PHF, and therefore would not produce much torsional strain on the AD-tau. The strain-relief mechanism may be a general theme of action of disruptors of amyloid fibrils, with strain arising from an initially formed metastable structure such as one with unfavorable twist, mismatched rise, or other energetically unfavorable interaction. In previous work, we presented evidence that the polyphenolic compound EGCG disassembles AD-tau by stacking into a metastable mock-amyloid fibril on the surface of AD-tau. A subsequent change in which aromatic rings of EGCG curve into a more stable conformation can provide the energy to disassemble stable AD-tau. Thus, both disassembling actions of the very different compounds EGCG and D-TLKIVWX (SEQ ID NO: 14) on amyloid fibrils may be considered examples of strain-relief mechanisms. This strain-relief mechanism may be applied to the design of a new generation of disaggregators for tau and other pathological amyloids and provides a new direction for the development of first-in-class therapeutics for neurodegenerative diseases. Methods Cryo-EM samples D-TLKIVWI (SEQ ID NO: 15) fibrils were optimized by shaking 4 mM D- TLKIVWI (SEQ ID NO: 15) in deionized water at room temperature for three days.10 mM D-TLKIVWS (SEQ ID NO: 10) / R in deionized water formed fibrils when left undisturbed for three days at room temperature. For D-TLKIVWR (SEQ ID NO: 16) fibrils, the pH of the peptide solution was adjusted to 7.0. Prior to cryo-EM grid preparation, AD-tau in a buffer comprised of 20 mM Tris-HCl pH 7.4, 100 mM NaCl were pre-incubated at 37 °C with final concentration of 100 µM D-TLKIVWX (SEQ ID NO: 14) (X = I, S, R) from 10 mM stocking solution in water for 24 hours. Control tau fibrils from the same brain donor were treated identically except for the addition of D-TLKIVWX (SEQ ID NO: 14). Cryo-EM data collection and processing To prepare the cryo-EM grids, we applied 2.5 μl of sample solution onto Quantifoil 1.2 / 1.3200 mesh electron microscope grids glow-discharged for 2 minutes in a Pelco easiGlow unit before use. Grids were plunge-frozen into liquid nitrogen- cooled liquid ethane inside a Vitrobot Mark IV (FEI) vitrification robot after blotting. Cryo-EM data of D-TLKIVWR (SEQ ID NO: 16) and D-TLKIVWS (SEQ ID NO: 10) fibrils were collected on a Titan Krios transmission electron microscope (Thermo Fisher Scientific) located at the National Center for Cryo-EM Access and Training, which is equipped with a Bioquantum / K3 direct detection camera (Gatan), operated with 300 kV acceleration voltage and an energy slit width of 20 eV, automated with Leginon software package39. Super-resolution movies were collected with a calibrated pixel size of 1.067 Å / pixel (0.5335 Å / pixel in super-resolution movie frames) and a dose per frame of ~1.5 e- / Å2. A total of 40 frames with a frame rate of 12 Hz were taken for each movie, resulting in a final dose of ~60 e- / Å2per image. D-TLKIVWI (SEQ ID NO: 15) fibrils were collected on a Titan Krios located at the HHMI Janelia Research Campus, which is equipped with a cold-FEG source (CFEG), a Selectris X energy filter and a Falcon 4i direct detection camera (TFS), operated with 300 kV acceleration voltage and an energy slit width of 6 eV, and automated with the SerialEM software package40. Electron Event Representation (EER) files were collected with a calibrated pixel size of 0.94 Å / pixel and a dose per raw frame of 0.0244 e- / Å2, resulting in 55 e- / Å2per image. AD-tau / D-TLKIVWX (SEQ ID NO: 14) (X = I, S and R) were collected similarly as D-TLKIVWI (SEQ ID NO: 15) fibrils, although manually targeted in SerialEM package. The AD-tau control was collected on a Titan Krios / Bioquantum / K3 setup located at the Stanford-SLAC Cryo-EM Center, operated with 300 kV acceleration voltage and an energy slit width of 20 eV, automated with EPU (TFS). Movies and EER files were motion-corrected in RELION and binned to pixel sizes according to Supplementary Table 1, 2 in Kou et al,. CTF estimation was performed using CTFFIND4. AD-tau & D-TLKIVWX (SEQ ID NO: 14) fibrils were manually picked using e2helixboxer.py from EMAN2. D-TLKIVWX (SEQ ID NO: 14) fibrils and AD-tau control particle picking was initially done manually using e2helixboxer.py from EMAN2 for about 100 images as a training set for crYOLO. CrYOLO was then trained with default parameters and was used to pick the rest of the images. Particle extraction, two-dimensional classification, three-dimensional classification, and 3D refinement were performed in RELION. Briefly, particles were initially extracted using a larger box size of 640 pixels with two-fold binning. For the datasets of D-TLKIVWX (SEQ ID NO: 14) fibrils, 2D classification with tau_fudge 2 was performed with all particles, and the first two abundant classes were grouped into two fibril polymorphs. Particles from each polymorph were selected and used for 3D classification with K=1 initially and then K=3, using a Gaussian cylinder as the initial model. The best 3D classes were used as the initial model for subsequent 3D classifications with smaller box size particles. We re-extracted particles from all micrographs using a box size of 640 pixels scaled down to a 320 pixels box size. To improve resolution, additional 2D classifications were performed, with tau_fudge starting at 2 and increased incrementally to 4 in the final iterations. We manually selected 320-pixel particles for each polymorph based on the 2D classification of 640-pixel particles. Two rounds of K=3 3D classification was performed. High- resolution gold-standard refinement was performed for each polymorph and the initial near-atomic resolution maps with refined helical parameters were generated. CTF refinement and Bayesian polishing were performed, and the final reconstructions were generated by one or two rounds of additional golden-standard refinement. The resolution of each reconstruction was estimated using the 0.143 Fourier shell correlation (FSC) resolution cutoff. For the datasets of AD-tau control and AD-tau & D-TLKIVWX (SEQ ID NO: 14) fibrils, 2D classification with tau_fudge starting at 2 and increased incrementally to 4 was performed with all particles, and the PHF-shaped classes were grouped into one polymorph and, selected and used for 3D classification with K=1 initially and then K=3, using a Gaussian cylinder as the initial model. The best 3D classes were used as the initial model for subsequent 3D classifications with smaller box size particles. We re- extracted particles from all micrographs using a box size of 640 pixels scaled down to a 432 pixels box size. To improve resolution, additional 2D classifications were performed, with tau_fudge starting at 2 and increased incrementally to 4 in the final iterations. We manually selected 432-pixel particles for PHF polymorph. Two rounds of K=33D classification was performed. High-resolution gold-standard refinement was performed for each polymorph and the initial near-atomic resolution maps with refined helical parameters were generated. CTF refinement and Bayesian polishing were performed, and the final reconstructions were generated by one or two rounds of additional golden-standard refinement. The resolution of each reconstruction was estimated using the 0.143 Fourier shell correlation (FSC) resolution cutoff. Part of the Cryo-EM data processing used Expanse GPU at San Diego Supercomputer Center through allocation BIO230174 from the Advanced Cyberinfrastructure Coordination Ecosystem. Atomic model building Our starting atomic model of D-TLKIVWI (SEQ ID NO: 15) was an ideal β- strand. It was manually adjusted to fit the electrostatic potential map using Coot and automated refinement was performed using Phenix. To facilitate good rotamer geometry, the initial building and refinement was performed using a map with handedness chosen so that the amino acid residues appeared to be levorotary rather than dextrorotary. In this way, we could take advantage of the rotamer library in Coot which exists for L-amino acids, but not for D-amino acids. In the final step of refinement, the map and coordinates were inverted to the correct hand, consistent with D-amino acids. The starting models for D-TLKIVWS (SEQ ID NO: 10) and D-TLKIVWR (SEQ ID NO: 16) were adapted from the refined D-TLKIVWI (SEQ ID NO: 15) structure. All atomic models were refined in successive rounds using Coot for manual building and Phenix for automated refinement. Our starting atomic model of the complex between AD-tau PHF and D- TLKIVWI (SEQ ID NO: 15) was built by manually orienting coordinates of the tau PHF (PDB ID 7nrv) to fit the electrostatic potential map using Coot and then refined with Phenix. Coordinates of a pair of β-sheets were extracted from the D-TLKIVWI (SEQ ID NO: 15) structure described above and manually docked on the surface of the PHF using guidance from the 3.1 Å cryoEM map, as well as the low-pass filtered map (7 Å). We noted a blob of residual density situated at the end of three lysine side chains: K317 and K321 of tau and K3 of the D-peptide. Whatever molecule produced this residual density does not depend on the presence of the D-peptide to bind to tau, since a similar blob was evident in our PHF negative control lacking D-peptide. Indeed, the presence of this residual density was noted in the original structure report of AD-tau PHFs, and even noted in maps from PHFs produced with recombinant tau (PDB ID 7ql4). The starting models for tau complexed with D-TLKIVWS (SEQ ID NO: 10) and D-TLKIVWR (SEQ ID NO: 16) were obtained using an analogous procedure. The final refined coordinates for these two complexes do not include the D-peptides because density for the peptides was visible only in the low-pass filtered maps, and not in the high-resolution map (Fig.31a-c). High-speed atomic force microscopy (HS-AFM) AD-tau (~1 μM, 10 µL) were deposited onto a mica surface, incubated for 15 minutes, and gently rinsed three times with 10 μL of disaggregation buffer. The mica was then immersed in 850 μL of 500 μM D-TLKIVWI (SEQ ID NO: 15). Disaggregation was analyzed using a NanoRacer High-Speed AFM (Bruker) in amplitude-modulation AC mode at an ambient temperature. For samples pre- incubated with D-TLKIVWI (SEQ ID NO: 15), AD-tau (~1 μM, 10 µL) were mixed with 500 μM D-TLKIVWI (SEQ ID NO: 15) for six hours before deposition on mica for HS-AFM characterization. INCORPORATION BY REFERENCE Each publication and patent mentioned herein (e.g., Hou et al., Science Advances, 1 May 2024 Vol 10, Issue 18; and Eisenberg et al., Research Square 8 May 2024) is hereby incorporated by reference in its entirety. In case of conflict, the present specification, including any definitions herein, will control. EQUIVALENTS While specific embodiments of the subject invention have been discussed, the above specification is illustrative and not restrictive. Many variations of the invention will become apparent to those skilled in the art upon review of the preceding description and the following claims. The full scope of the invention should be determined by reference to the claims, along with their full scope of equivalents, and by reference to the rest of the specification, along with such variations.

Claims

CLAIMS What is claimed is:

1. An agent comprising: a) a binding and / or disaggregating moiety that adheres to a target polypeptide in its amyloid fibril form, and proceeds to inhibit the target protein and / or disaggregate the fibril form, and b) a nanomass moiety that promotes transfer of the agent to a site of the target polypeptide.

2. The agent of claim 1, wherein the binding and / or disaggregating moiety is a peptidic compound that inhibits aggregation of the target polypeptide and / or disassembles a target polypeptide aggregate, and the nanomass moiety comprises a magnetic nanoparticle, wherein the target polypeptide comprises a protein sequence within an amyloid fibril.

3. The agent of claim 2, wherein the peptidic compound comprises one or more D-amino acid residues.

4. The agent of any one of the preceding claims, wherein the target polypeptide is a tau amyloid fibril.

5. The agent of claim 2, wherein the peptidic compound: is selected from D-TLKIVWC (SEQ ID NO: 2) , D-TLKIWWX1 (SEQ ID NO: 3) , wherein X1 is a single D-amino acid reissue or a string of D-amino acid residues, D-TWKLVLC (SEQ ID NO: 4) , D-YVIIERC (SEQ ID NO: 5) , D- DYYFEFC (SEQ ID NO: 6) , L-SVWIWYE (SEQ ID NO: 7) , L-DVQMINKKLK (SEQ ID NO: 8) , and a combination thereof; or comprises D-TLKIVWX2 (SEQ ID NO: 9) , wherein X2is a single D-amino acid selected from alanine (A), serine (S), isoleucine (I), valine (V), arginine (R), lysine (K), glutamic acid (E), Aspartic Acid (D), proline (P) and threonine (T).

6. The agent of claim 2, wherein the magnetic nanoparticle comprises a coating that comprises polyethylene glycol (PEG), dextran, starch, chitosan, lipid, citrate,polyaniline, meso-2,3-dimercaptosuccinic acid, poly(maleic anhydride-alt-1- octadecene), polyacrylamide, phosphonate, silica, a protein or a peptide segment having a sequence that is recognized by membrane-embedded proteins in the brain endothelium for conveying the agent across the blood-brain barrier, or a combination thereof.

7. The agent of claim 6, the coating comprises dextran, and wherein the dextran comprises dextran-20kDa, dextran-40kDa, carboxy dextran, cross-linked dextran- 20kDa, or a combination thereof.

8. The agent of claim 2, wherein the magnetic nanoparticle is an iron oxide nanoparticle (IONP).

9. The agent of claim 2, wherein the nanoparticle has a hydrodynamic particle size from about 4 nanometers to about 200 nanometers as measured by dynamic light scattering.

10. The agent of claim 1, wherein the agent destabilizes a tau amyloid fibril when in contact with said tau amyloid fibril.

11. The agent of claim 1, wherein the agent is permeable across the blood-brain barrier.

12. A composition comprising a plurality of agents of claim 1.

13. The composition of claim 12, wherein the composition is for treating a condition associated with polypeptide aggregation.

14. The composition of claim 13, wherein the condition is associated with tau protein fibrillation.

15. The composition of claim 12, further comprising a pharmaceutically acceptable excipient.

16. The composition of claim 15, wherein the excipient increases membrane permeability to peptides.

17. A method of preparing the agent of claim 1, wherein the method comprises: reacting a dextran coated magnetic nanoparticle coupled to at least one – COOH group with maleimide-CH2-NH2 in presence of N-ethyl-N′-(3- (dimethylamino)propyl)carbodiimide (EDC) and N-hydroxysulfosuccinimide (Sulfo-NHS), thereby forming a maleimide-magnetic nanoparticle, and reacting the maleimide-magnetic nanoparticle with a peptidic compound comprising one or more D-amino acid residues and a C-terminal cysteine, thereby forming the agent.

18. A method for treating or preventing a condition associated with polypeptide aggregation in a subject in need thereof, comprising administering the agent of claim or the composition of claim 12 to the subject, thereby treating or preventing the condition.

19. The method of claim 18, wherein the condition is associated with tau protein fibrillation.

20. The method of claim 18, wherein said administering comprises administering intravenously, intranasally, or intramuscularly.

21. The method of claim 18, wherein the condition comprises Alzheimer's disease.

22. The method of any one of claim 18, wherein the condition comprises progressive supranuclear palsy or chronic traumatic encephalopathy or other tauopathy.

23. A method for diagnosing a condition associated with polypeptide aggregation in a subject in need thereof, comprisingadministering the agent of claim 1 or the composition of claim 12 to the subject, thereby treating the condition; scanning the subject by a magnetic resonance imaging (MRI) spectroscopy to get an MRI scan; and diagnostically processing the MRI scan derived from magnetic resonance imaging (MRI) spectroscopy.

24. The method of claim 23, wherein the condition is associated with tau protein fibrillation.

25. The method of claim 23, wherein said administering comprises administering intravenously, intranasally, or intramuscularly.

26. The method of claim 23, wherein the condition comprises Alzheimer's disease.

27. The method of claim 23, wherein the condition comprises progressive supranuclear palsy or chronic traumatic encephalopathy or other tauopathy.

28. The method of claim 18, wherein the subject is a human.

29. A method of destabilizing a tau amyloid fibril, comprising contacting the tau amyloid fibril with the agent of claim 1.

30. A peptidic compound that inhibits aggregation of a target polypeptide, wherein the target polypeptide comprises a zipper sequence, the peptidic compound comprising: a binding and / or a disaggregating moiety comprising one or more D- amino acid residues that binds to the target polypeptide in its amyloid fibril state and a delivery moiety comprising a nanoparticle, wherein the peptidic compound comprises at least seven amino acid residues.

31. The peptidic compound of claim 30, wherein the target polypeptide is a tauamyloid fibril.

32. The peptidic compound of claim 30, wherein the peptidic compound is D- TLKIVWC (SEQ ID NO: 2) , D-TLKIVWS (SEQ ID NO: 10) , D-TLKIVWA (SEQ ID NO: 11) , D-TLKIVWD (SEQ ID NO: 12) , or a combination thereof.

33. A composition comprising at least one peptidic compound of claim 30.

34. The composition of claim 33, wherein the composition is for treating a condition associated with polypeptide aggregation.

35. The composition of claim 34, wherein the condition is associated with tau protein fibrillation.

36. The composition of claim 33, further comprising a pharmaceutically acceptable excipient.

37. The composition of claim 36, wherein the excipient increases membrane permeability to peptides.

38. A method for treating or preventing a condition associated with polypeptide aggregation in a subject in need thereof, comprising administering the peptidic compound of claim 30 or the composition of claim 33 to the subject, thereby treating or preventing the condition.

39. The method of claim 38, wherein the condition is associated with tau protein fibrillation.

40. The method of claim 38, wherein said administering comprises administering intravenously, intranasally, or intramuscularly.

41. The method of claim 38, wherein the condition comprises Alzheimer's disease.

42. The method of claim 38, wherein the condition comprises progressive supranuclear palsy or chronic traumatic encephalopathy or other tauopathy.

43. A method for diagnosing a condition associated with polypeptide aggregation in a subject in need thereof, comprising administering the peptidic compound of claim 30 or the composition of claim 33 to the subject, thereby treating the condition; scanning by a magnetic resonance imaging (MRI) spectroscopy to get an MRI scan; and diagnostically processing the MRI scan derived from magnetic resonance imaging (MRI) spectroscopy.

44. The method of claim 43, wherein the condition is associated with tau protein fibrillation.

45. The method of claim 43, wherein said administering comprises administering intravenously, intranasally, or intramuscularly.

46. The method of claim 43, wherein the condition comprises Alzheimer's disease.

47. The method of claim 43, wherein the condition comprises progressive supranuclear palsy or chronic traumatic encephalopathy or other tauopathy.

48. The method of claim 38, wherein the subject is a human.

49. A method of destabilizing a tau amyloid fibril, comprising contacting the tau amyloid fibril with the peptidic compound of claim 30.

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