Use of a polypeptide in preparing a drug / reagent for preventing and treating Alzheimer's disease

Abstract

The invention discloses a use of a polypeptide in the preparation of a drug / reagent for preventing and treating Alzheimer's disease, and relates to the field of biomedicine. The polypeptide comprises the 31-71 amino acids of the extracellular segment of the TREM2 receptor protein, and its amino acid sequence is shown in SEQ ID NO: 1, and its nucleotide sequence is shown in SEQ ID NO: 2. The polypeptide can be used in the preparation of drugs for preventing and treating diseases related to complement disorders. The polypeptide can bind to the complement protein C1q, can inhibit the classical complement cascade reaction, and has the effects of reducing the deposition of complement protein C3 in the brain of a neurodegenerative disease model mouse, reducing the phagocytosis of synapses by microglia, increasing the density of synaptic proteins, and improving synaptic function and learning and memory ability, so it can be used in the preparation of inhibitors of the classical complement pathway, and has the use of preparing drugs for preventing and treating diseases related to complement disorders.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine, and in particular to use of a polypeptide in preparing a drug / reagent for preventing and treating Alzheimer's disease. Background Art

[0002] The complement system is an important part of the human innate immunity. In recent years, people have found that in addition to assisting antibodies in exerting immune effects, complement is also involved in inflammation, neurodegenerative diseases, and cancer. The complement system is composed of a large number of proteins. In addition to the classic components of the complement cascade C1-C9, it also contains more than 50 other proteins. These proteins form a complex regulatory network that mediates immune surveillance and tissue homeostasis. Under normal physiological conditions, complement proteins exist in body fluids in an inactive form. Under the action of certain activators, complement is activated through cascade enzymatic reactions and exerts biological activity. The complement system can be activated by the classical pathway (CP), the lectin pathway (LP), and the alternative pathway (AP). Their activation initiators are different, but they all converge on the third component of complement (C3) and lead to the production of effector molecules. The complement cascade can supplement the clearance ability of antibodies and phagocytes to invading microorganisms through the opsonization of C3b; promote inflammatory responses through C3a and C5a; and dissolve pathogens through the C5b-9 membrane attack complex. The complement system works together with other immune and physiological systems to integrate innate immunity and adaptive immunity, jointly mediating the clearance of immune complexes, cell debris and apoptotic cells, promoting the development of normal tissues and organs and tissue repair after injury.

[0003] Although complement activation can effectively protect the body from pathogen invasion and infection, excessive or dysregulated complement activation may lead to a series of diseases. At present, a variety of acute and chronic diseases caused by complement disorders have been found. Acute diseases include antibody-mediated immune rejection, sepsis, ischemic stroke, etc., and chronic diseases include autoimmune diseases, cancer, kidney disease, chronic hemolytic disease, periodontal disease, eye disease, and neurodegenerative diseases. Since complement system disorders cause the occurrence of many diseases, the development of drugs targeting the complement system has received widespread attention.

[0004] C1q is the core component of complement C1 and the initiator of the classical complement cascade. Abnormal activation of C1 can trigger microglia to recognize and phagocytose complement-labeled synapses, ultimately leading to synaptic loss and neurodegeneration. In several animal models of diseases such as Alzheimer's disease, Huntington's disease, frontotemporal dementia, and glaucoma, knocking out the C1q gene can inhibit the loss of synapses and improve the behavioral performance of mice, suggesting that inhibiting C1q has protective significance for the above diseases. At present, stereotaxic injection of C1q-specific antibodies has been shown to significantly improve the pathology of mice with a variety of neurodegenerative disease models, but these antibodies have a large molecular weight and are difficult to cross the blood-brain barrier. Therefore, there are no available neurodegenerative disease intervention drugs targeting complement C1q in clinical practice. Summary of the invention

[0005] The first object of the present invention is to provide a polypeptide TREM231-71.

[0006] The second object of the present invention is to provide the use of the polypeptide in preparing drugs for preventing and treating diseases related to complement disorders.

[0007] The present invention provides a polypeptide TREM231-71, comprising amino acids 31-71 of the extracellular segment of a TREM2 receptor protein, wherein the amino acid sequence thereof is shown in SEQ ID NO: 1, and the nucleotide sequence thereof is shown in SEQ ID NO: 2.

[0008] The present invention provides use of the polypeptide in preparing medicines for preventing and treating diseases related to complement disorders.

[0009] The complement is C1, which is composed of three glycoprotein subunits: C1q, C1r, and C1s.

[0010] The diseases associated with complement disorder include neurodegenerative diseases with amyloid pathology or tau pathology, or diseases caused by excessive accumulation of complement protein C1q.

[0011] The polypeptide has the purpose of binding to complement protein C1q.

[0012] The polypeptide has the purpose of inhibiting the cleavage of complement protein C1 to C2.

[0013] The present invention provides the use of the polypeptide in preparing a classical complement pathway inhibitor. The polypeptide has the function of inhibiting the activation of the classical complement pathway.

[0014] The present invention provides application of the polypeptide in drugs for preventing and treating brain neurodegenerative diseases, brain damage and brain dysfunction diseases.

[0015] The polypeptide has the function of inhibiting the deposition of complement protein C3 in the brain of patients with neurodegenerative diseases.

[0016] The polypeptide has the function of reducing the phagocytosis of neural synapses by microglia in the brain of neurodegenerative diseases.

[0017] The polypeptide has the function of increasing the density of synaptic proteins in the brain with neurodegenerative diseases.

[0018] The polypeptide has the function of increasing the synaptic function in the brain with neurodegenerative diseases.

[0019] The present invention provides the use of the polypeptide in a drug for preventing and / or alleviating learning and memory dysfunction caused by Alzheimer's disease. The polypeptide has the function of increasing the learning and memory function of neurodegenerative diseases.

[0020] Compared with the existing technology of targeted intervention using complement-specific antibodies, the present invention is a polypeptide containing 41 amino acids, which is easier to penetrate the blood-brain barrier and enter the brain than antibodies to inhibit complement activity, so the polypeptide has good application prospects in the treatment of neurodegenerative diseases. In addition, the present invention reports for the first time that the TREM231-71 polypeptide can improve complement disorder-related diseases, which is specifically embodied in that the TREM231-71 polypeptide can bind to the complement protein C1q, inhibit the cleavage of C2 by C1, and inhibit the classical complement cascade reaction. By stereotaxic brain injection or tail vein injection of TREM231-71 polypeptide into neurodegenerative disease model mice, C3 protein deposition can be significantly reduced, microglia phagocytosis of synapses can be reduced, synaptic protein density can be increased, and synaptic function and learning and memory ability can be improved. Therefore, the TREM231-71 polypeptide can be used in the preparation of classical complement pathway inhibitors, and will have broad application prospects in the preparation of drugs for the prevention and treatment of complement disorder-related diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 is a graph showing the results of TREM231-71 polypeptide binding to complement C1q;

[0022] Figure 2 This is a graph showing the results of TREM231-71 peptide inhibiting activation of the classical complement pathway;

[0023] Figure 3 This is a graph showing the results of the TREM231-71 polypeptide inhibiting the cleavage of C2 by C1;

[0024] Figure 4 This is a graph showing the results of TREM231-71 polypeptide reducing the level of C3 protein in the brain of mice with amyloid disease;

[0025] Figure 5 This is a graph showing the results of TREM231-71 peptide reducing C3 deposition in the brains of mice with amyloid disease;

[0026] Figure 6 This is a diagram showing the results of TREM231-71 peptide reducing the phagocytosis of synapses by microglia in the brains of mice with amyloid disease;

[0027] Figure 7 This is a graph showing the results of TREM231-71 peptide increasing the level of synaptic proteins in the brain of mice with amyloid disease;

[0028] Figure 8 This is a graph showing the results of TREM231-71 peptide improving the synaptic function of mice with amyloid disease;

[0029] Fig. 9 This is a graph showing the results of TREM231-71 peptide reducing the level of C3 protein in the brain of mice with Tau protein disease;

[0030] Fig.10 This is a graph showing the results of TREM231-71 peptide reducing C3 deposition in the brains of mice with Tau protein disease;

[0031] Fig.11 This is a diagram showing the results of TREM231-71 peptide reducing the phagocytosis of synapses by microglia in the brains of mice with Tau protein disease;

[0032] Fig.12 This is a graph showing the results of TREM231-71 peptide increasing the level of synaptic proteins in the brains of mice with Tau protein disease;

[0033] Fig.13 This is a graph showing the results of TREM231-71 peptide reducing cognitive deficits in mice with Tau protein disease. DETAILED DESCRIPTION

[0034] Embodiments of the present invention are described in detail below, and the examples of the embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals represent the same or similar elements or elements with the same or similar functions from beginning to end. The embodiments described below by reference to the accompanying drawings are exemplary, are intended to be used to explain the present invention, and are not to be construed as limitations of the present invention. Those who do not indicate specific techniques or conditions in the embodiments are carried out according to the techniques or conditions described in the documents in this area or according to the product specification. Those who do not indicate the manufacturer of reagents or instruments used are all conventional products that can be obtained commercially.

[0035] Example 1 Obtaining TREM231-71 polypeptide

[0036] Triggering receptor expressed on myeloid cells 2 (TREM2) belongs to the Ig (Immunoglobulin, Ig) superfamily. Its encoding gene is located on chromosome 6p21, and the encoded nucleotide and amino acid sequences are numbered NM_018965.3 in Genbank. The present invention uses sequence truncation experiments to screen and obtain amino acids 31-71 of the extracellular segment of the TREM2 protein, mediating the binding of TREM2 to C1q. The polypeptide sequence obtained by entrusting Kesheng Jingpeptide Company to synthesize is as follows:

[0037] The amino acid sequence of TREM2 31-71 is:

[0038] SLQVSCPYDSMKHWGRRKAWCRQLGEKGPCQRVVSTHNLWL SEQ ID NO: 1

[0039] The nucleotide sequence of TREM231-71 is:

[0040] TCCCTGCAGG TGTCTTGCCC CTATGACTCC ATGAAGCACT GGGGGAGGCG CAAGGCCTGGTGCCGCCAGC TGGGAGAGAA GGGCCCATGC CAGCGTGTGG TCAGCACGCA CAACTTGTGG CTG SEQ IDNO: 2

[0041] Example 2 Detection of the binding ability of TREM231-71 polypeptide and complement C1q

[0042] Reference Figure 1, the binding ability of TREM231-71 peptide and scrambled peptide as control to C1q was detected by enzyme-linked immunosorbent assay (ELISA). TREM231-71 peptide and Scrambled peptide were synthesized at Keshengjing Peptide Co., Ltd. 10 μM TREM231-71 peptide and Scrambled peptide were fixed in a 96-well plate, sealed with plastic film, and shaken at 4°C overnight. On the second day, the liquid in the plate was discarded, and the plate was washed three times with 0.1% PBST (1×PBS+0.1% Tween 20), and then blocked with 4% BSA in a 37°C oven for 1 h. Different concentrations of C1q protein (0, 0.78125, 1.5625, 3.125, 6.25, 12.5, 25, 50 nM) were added, and C1q was diluted in 1×PBS and incubated at 37°C for 1 h; after washing three times with 0.1% PBST, the plate was blocked with C1q biotinylated antibody (Hycult Biotech, HM1096BT, 1: 200) was incubated in a 37°C oven for 1 hour; after the primary antibody incubation, the plate was washed and then the streptavidin Poly-HRP40 coupling reagent (Fitzgerald, 65R-S104PHRP, 1: 3000) was added and incubated at 37°C for 30 minutes; after washing three times with 0.1% PBST, TMB (SigmaAldrich, T5569) was used for color development, and the absorbance at 656nm was recorded. The results showed that the Scrambled peptide did not bind to C1q, and the TREM231-71 peptide had a strong interaction with C1q, and the equilibrium dissociation constant KD value of its binding was 1.41nM.

[0043] Example 3 Effect of TREM231-71 polypeptide binding to complement C1q on complement pathway activation

[0044] Human IgM was used to specifically activate the classical complement pathway, and then ELISA was used to detect C3 deposition to assess complement activation levels. Human IgM (Calbiochem, 4017991MG, 2 μg / mL) dissolved in 75 mM sodium carbonate (pH 9.6) was added to the ELISA plate and incubated overnight at 4°C. The plate was washed three times with 0.1% PBST the next day. GVB was used to detect C3 deposition in the ELISA plate. ++(Gelatin Veronal Buffer, Complement Technology, B100) was used to dilute normal human serum (Normal Human Serum, Complement Technology, NHS), and then different concentrations of Scrambled or TREM231-71 peptides were added and incubated at 4°C for 2h, and then added to the plate and incubated at 37°C for 25min. The plate was washed three times with 0.1% PBST, and C3 antibody (Santa Cruz, sc-20137, 1:100) was added and incubated at room temperature for 1h. The plate was washed three times with 0.1% PBST, and HRP-labeled secondary antibody (ThermoFisher Scientific, 31460, 1:2000) was added and incubated at room temperature for 40min. Finally, TMB was added for color development and the absorbance value of each well at 656nm was recorded. Figure 2 The results of the inhibition of complement C3 deposition by TREM231-71 polypeptide are shown in the figure, and the results show that: TREM231-71 polypeptide significantly inhibits the deposition of complement protein C3.

[0045] Example 4 Effect of the Binding of TREM231-71 Peptide and Complement C1q on C1 Cleavage of C2

[0046] TREM231-71 peptide (10 μM) or C1 esterase inhibitor (C1-INH) (Peprotech, 130-20, 5 μg / mL) and C1 protein (Complement Technology, A098, 0.1 μg / mL) were added to GVB ++ The samples were incubated at 4°C for 2 h in the buffer, and then C2 protein (Complement Technology, A112, 2 μg / mL) was added and incubated at 37°C for 1 h. C1-INH was used as a positive control. Finally, an equal volume of 2×SDS loading buffer without DTT was added to terminate the cleavage reaction, and the samples were boiled at 100°C for 10 min. The level of C2 cleavage products was analyzed by Western blotting. The results are shown in Figure 3 Compared with the control group, the TREM231-71 polypeptide reduced the cleavage efficiency of C2 by C1 by 27.10%, indicating that the TREM231-71 polypeptide can significantly inhibit the cleavage of C2 by C1.

[0047] Example 5 Effect of TREM231-71 polypeptide on complement C3 protein levels in the brain of amyloid lesion model mice

[0048] Six 7-month-old amyloid disease model mice, 5xFAD mice, were taken. After isoflurane anesthesia, they were placed on a brain stereotaxic instrument, the scalp was carefully cut to find the position of the anterior fontanel, and the position was found with the anterior fontanel as the origin (hippocampal area: ±2.0mm, -2.0mm), and a hole was made at this position. The polypeptide was injected with a microsyringe at a speed of 0.2μL / min and a depth of 2.0mm. The Scrambled control polypeptide and TREM231-71 polypeptide (i.e., the polypeptide synthesized in Example 1) were injected into the left and right hemispheres, respectively, with a protein concentration of 5μg / μL, and 2μL was injected each. After the injection, the needle was allowed to stay for 5 minutes to allow the polypeptide to fully diffuse, the syringe was slowly withdrawn, the wound was sutured and erythromycin was applied, and the mice were returned to the breeding cage for breeding. Seven days after the injection, the brain tissue was collected for homogenization and lysis, and the changes in complement C3 were detected by immunoblotting (Abcam, ab200999, 1:1000). The results are as follows Figure 4 As shown, compared with the Scrambled control peptide, the TREM231-71 peptide reduced the levels of C3 and iC3b proteins by 37.40% and 45.44%, respectively. The above results show that after the TREM231-71 peptide is injected into the hippocampus, it can significantly reduce the levels of C3 and iC3b proteins in the hippocampus of mice.

[0049] Example 6 Effect of TREM231-71 polypeptide on complement C3 deposition in the brain of amyloid disease model mice

[0050] The use of mice and the injection method were the same as in Example 4. Seven days after the injection, the mouse brains were collected and fixed overnight in 4% PFA, then dehydrated with 25% and 30% sucrose, and finally embedded in OCT and frozen sections were made. Complement protein C3 was immunofluorescently stained (Abcam, ab200999, 1:100) and the deposition level of complement protein C3 was counted. The results are shown in Figure 5 As shown, the C3 deposition in the group injected with Scrambled control peptide was 0.14 / μm 2 , the C3 deposition in the group injected with TREM231-71 was 0.10 / μm 2 The above results show that after the TREM231-71 peptide is injected into the hippocampus, it can significantly reduce the deposition of C3 protein in the hippocampus of mice.

[0051] Example 7 Effect of TREM231-71 polypeptide on phagocytosis of synapses by microglia in the brain of mice with amyloid disease model

[0052] The use of mice and the injection method were the same as in Example 5. Seven days after the injection, the mouse brains were collected and fixed overnight in 4% PFA, then dehydrated with 25% and 30% sucrose, and finally embedded in OCT and frozen sections were made. Immunofluorescence staining of microglia Iba1 (Wako, 019-19741, 1:200) and synaptic protein PSD95 (EDM Millipore, MAB1596, 1:100) was performed. The co-localization of PSD95 and Iba1 was statistically analyzed to reflect the level of microglia phagocytosis of synapses. The results are shown in Figure 2. Figure 6 As shown, the percentage of phagocytosis of synapses by microglia in the group injected with Scrambled control peptide was 3.29%, and the percentage of phagocytosis of synapses by microglia in the group injected with TREM231-71 was 2.23%. The above results show that after the TREM231-71 peptide is injected into the hippocampus, it can significantly reduce the phagocytosis of synapses by microglia in the hippocampus of 5xFAD mice.

[0053] Example 8 Effect of TREM231-71 polypeptide on synaptic protein levels in the brain of amyloid disease model mice

[0054] The use of mice and the injection method were the same as in Example 5. Seven days after the injection, the mouse brains were collected and fixed overnight in 4% PFA, then dehydrated with 25% and 30% sucrose, and finally embedded in OCT and frozen sections were made. The synaptic protein PSD95 was immunofluorescently stained (EDM Millipore, MAB1596, 1:100), and the density of the synaptic protein PSD95 was counted. The results are shown in Figure 7 As shown, the PSD95 density of the Scrambled control peptide injection group was 0.38 / μm 2 , the PSD95 density of the TREM231-71 injection group was 0.43 / μm 2 The above results show that after the TREM231-71 peptide is injected into the hippocampus, it can significantly increase the density of the synaptic protein PSD95 in the hippocampus of mice.

[0055] Example 9 Effect of TREM231-71 polypeptide on synaptic function in amyloid disease model mice

[0056] The use of mice and the injection method were the same as in Example 6. Seven days after the injection, the brain was acutely harvested and the changes in miniature excitatory postsynaptic current (mEPSC) in the hippocampus of 5xFAD mice were detected by electrophysiology. Figure 8As shown, the mEPSC frequency and amplitude of the Scrambled control peptide injection group were 0.46Hz and 7.65pA, respectively, and the mEPSC frequency and amplitude of the TREM231-71 peptide injection group were 0.78Hz and 8.60pA, respectively. The above results show that after the TREM231-71 peptide is injected into the hippocampus, it can increase the frequency and amplitude of mEPSC of excitatory neurons in the hippocampus of 5xFAD mice, indicating that the TREM231-71 peptide can improve the synaptic function of 5xFAD mice.

[0057] Example 10 Effect of TREM231-71 polypeptide on complement C3 protein levels in the brain of Tau protein pathology model mice

[0058] Eight-month-old Tau protein disease model mice, PS19, were selected for tail vein injection experiments (50 μg of Scrambled control peptide and TREM231-71 peptide were injected into each mouse each time, once every 3 days). After 30 days of injection, brain tissues were collected for homogenization and lysis, and changes in complement C3 were detected by immunoblotting (Abcam, ab200999, 1:1000). Fig. 9 As shown, compared with the Scrambled control peptide, the TREM231-71 peptide reduced the levels of C3 and iC3b proteins by 46.74% and 38.44%, respectively. The above results show that after the TREM231-71 peptide is injected into the hippocampus, it can significantly reduce the levels of C3 and iC3b proteins in the hippocampus of mice.

[0059] Example 11 Effect of TREM231-71 polypeptide on complement C3 deposition in the brain of Tau protein pathology model mice

[0060] The use of mice and the injection method were the same as in Example 10. 30 days after the injection, the mouse brains were collected and fixed overnight in 4% PFA, then dehydrated with 25% and 30% sucrose, and finally embedded in OCT and frozen sections were made. Immunofluorescence staining of complement protein C3 (Abcam, ab200999, 1:100) was performed to count the deposition level of complement protein C3. The results are shown in Figure 2. Fig.10 As shown, the C3 deposition in the group injected with Scrambled control peptide was 0.30 / μm 2 , the C3 deposition in the TREM231-71 injection group was 0.27 / μm 2 The above results show that after the TREM231-71 peptide is injected into the hippocampus, it can significantly reduce the deposition of C3 protein in the hippocampus of mice.

[0061] Example 12 Effect of TREM231-71 polypeptide on phagocytosis of synapses by microglia in the brain of mice with Tau protein pathology

[0062] The use of mice and the injection method were the same as in Example 10. 30 days after the injection, the mouse brains were collected and fixed overnight in 4% PFA, then dehydrated with 25% and 30% sucrose, and finally embedded in OCT and frozen sections were made. Immunofluorescence staining of microglia Iba1 (Wako, 019-19741, 1:200) and synaptic protein PSD95 (EDM Millipore, MAB1596, 1:100) was performed. The co-localization of PSD95 and Iba1 was statistically analyzed to reflect the level of microglia phagocytosis of synapses. The results are shown in Figure 2. Fig.11 As shown, the percentage of phagocytosis of synapses by microglia in the group injected with Scrambled control peptide was 2.34%, and the percentage of phagocytosis of synapses by microglia in the group injected with TREM231-71 was 1.53%. The above results show that after the TREM231-71 peptide is injected into the hippocampus, it can significantly reduce the phagocytosis of synapses by microglia in the hippocampus of mice with Tau protein pathology model.

[0063] Example 13 Effect of TREM231-71 polypeptide on synaptic protein levels in the brain of Tau protein disease model mice

[0064] The use of mice and the injection method were the same as in Example 10. Thirty days after the injection, the brain tissue was collected and homogenized, and the levels of postsynaptic protein PSD95 (Cell Signaling Technology, 3450S, 1:2000) and presynaptic protein vGluT1 (Millipore, MAB5502, 1:2000) were detected by immunoblotting. Fig.12 As shown, compared with the group injected with the Scrambled control peptide, the density of PSD95 and vGluT1 in the group injected with TREM231-71 increased by 1.53 and 1.33 times, respectively. The above results show that after the TREM231-71 peptide is injected into the hippocampus, it can significantly increase the protein levels of synaptic proteins PSD95 and vGluT1 in the hippocampus of mice.

[0065] Example 14 TREM231-71 polypeptide alleviates cognitive deficits in Tau protein pathology model mice

[0066] The use and injection methods of mice were the same as those in Example 10. Thirty days after the injection, novel object recognition and water maze tests were performed to detect the learning and memory abilities of the mice. Fig.13As shown: PS19 mice injected with Scrambled control peptides spent an average of 53.21 seconds exploring new objects, and PS19 mice injected with TREM231-71 spent an average of 93.77 seconds exploring new objects. The results of the water maze experiment showed that the number of platform shuttles within 60 seconds for PS19 mice injected with Scrambled control peptides was 1.46, and the number of platform shuttles within 60 seconds for PS19 mice injected with TREM231-71 was 2.23. The above results show that tail vein injection of 31-71 peptides can alleviate the cognitive deficits of Tau protein disease model mice.

[0067] In summary, TREM231-71 polypeptide can improve complement-related disorders, which is specifically reflected in the following aspects: TREM231-71 polypeptide can bind to complement protein C1q, inhibit C1 from cleaving C2, and inhibit the classical complement cascade reaction. By stereotaxic brain injection or tail vein injection of TREM231-71 polypeptide into neurodegenerative disease model mice, the deposition of C3 protein can be significantly reduced, the phagocytosis of synapses by microglia can be reduced, the density of synaptic protein PSD95 can be increased, and the function of synapses and the learning and memory ability of mice can be improved. Therefore, TREM231-71 polypeptide can be used in the preparation of classical complement pathway inhibitors, and will have broad application prospects in the preparation of drugs for the prevention and treatment of diseases related to complement disorders.

[0068] Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are exemplary and are not to be construed as limitations on the present invention. A person skilled in the art may change, modify, substitute and modify the above embodiments within the scope of the present invention without departing from the principles and purpose of the present invention.

Claims

1. Use of a polypeptide having an amino acid sequence as shown in SEQ ID NO: 1 in the preparation of a drug for preventing and treating Alzheimer's disease.

2. The use according to claim 1, characterized in that The polypeptide has the function of inhibiting the deposition of complement protein C3 in the brain of Alzheimer's disease, the polypeptide has the function of reducing the phagocytosis of neural synapses by microglia in the brain of Alzheimer's disease, the polypeptide has the function of increasing the density of neural synaptic proteins in the brain of Alzheimer's disease, and the polypeptide has the function of increasing the electrophysiological activity of neurons in the brain of Alzheimer's disease.

3. Use of a polypeptide having an amino acid sequence as shown in SEQ ID NO: 1 in the preparation of a drug for preventing, treating and / or alleviating learning and memory dysfunction caused by Alzheimer's disease, wherein the polypeptide has the function of increasing the learning and memory function of Alzheimer's disease.

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