# US 2021/0329894 A1 · Method for preparing alzheimer's disease (ad) animal model

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- Number: US 2021/0329894 A1
- Document ID: US20210329894A1
- Status: Published application
- Kind: A1
- Application number: 17/125,368
- Filed: 2020-12-17
- Published: 2021-10-28
- Earliest claimed: 2020-04-28
- Assignees: Shanxi Medical University
- Applicants: Shanxi Medical University
- Inventors: Qiao NIU; Xiujun QIN; Liang LI
- Web page: https://patentgrep.com/patent/US20210329894A1

## CPC

- A01K 67/0275: Genetically modified vertebrates, e.g. transgenic
- A01K 67/0276: Knock-out vertebrates
- A01K 67/0278: Knock-in vertebrates, e.g. humanised vertebrates
- A01K 2207/15: Humanized animals
- A01K 2207/20: Animals treated with compounds which are neither proteins nor nucleic acids
- A01K 2217/056: due to mutation of coding region of the transgene (dominant negative)
- A01K 2217/072: maintaining or altering function, i.e. knock in
- A01K 2217/206: Animal model comprising tissue-specific expression system, e.g. tissue specific expression of transgene, of Cre recombinase
- A01K 2217/30: Animal model comprising expression system for selective cell killing, e.g. toxins, enzyme dependent prodrug therapy using ganciclovir
- A01K 2227/105: Murine
- A01K 2267/0312: Animal model for Alzheimer's disease
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS

## Abstract

The present disclosure relates to a method for preparing an Alzheimer's disease (AD) animal model, including: selecting healthy male human ApoE4 transgenic mice, and intraperitoneally injecting a 4 mmol/L Al(mal)3 solution at a volume of 10 ml/kg, with aluminum exposure for 60 days, and interval time of 2 days for every 5 days, to obtain an AD animal model co-induced by genetic and environmental factors which are interacted without being simply superimposed. The AD animal model established according to the method of the examples in the present disclosure can express the characteristic pathological changes of AD and has the characteristics of learning and memory impairment. The AD animal model provided by the present disclosure can be used for drug screening and AD mechanism research, and has the advantages of stable properties, prominent reproducibility, easy operation, and low cost.

## Claims

### Claim 1

A method for preparing an Alzheimer's disease (AD) animal model, comprising: selecting healthy male human ApoE4 transgenic mice, and intraperitoneally injecting a Al(mal)3 solution to obtain the AD animal model.

### Claim 2 (depends on 1)

The method according to claim 1, wherein, the human ApoE4 transgenic mice express human apolipoprotein E4 subtype but not endogenous mouse ApoE under the control of a human glial fibrillary acidic protein (GFAP) promoter, with insertion of human ApoE4 gene into mouse chromosome 15.

### Claim 3 (depends on 1)

The method according to claim 1, wherein, the human ApoE4 transgenic mice are healthy male mice aged 4 to 5 weeks.

### Claim 4 (depends on 2)

The method according to claim 2, wherein, the human ApoE4 transgenic mice are healthy male mice aged 4 to 5 weeks.

### Claim 5 (depends on 1)

The method according to claim 1, wherein, an 8 mmol/L aluminum chloride solution and a 24 mmol/L maltol solution are prepared with sterilized triple distilled water, then the two solutions are mixed in a volume ratio of 1:1 to obtain a Al(mal)3 solution with a final concentration of 4 mmol/L, and pH is adjusted to 7.4 with 10% NaOH.

### Claim 6 (depends on 1)

The method according to claim 1, wherein, the 4 mmol/L Al(mal)3 solution is intraperitoneally injected at a volume of 10 ml/kg, with aluminum exposure for 60 days, and interval time of 2 days for every 5 days.

### Claim 7 (depends on 1)

The method according to claim 1, wherein, the steps also comprise evaluation of the AD animal model, comprising a Morris water maze experiment and a new object recognition task.

### Claim 8 (depends on 7)

The method according to claim 7, wherein, the evaluation of the AD animal model also comprises determination of aluminum content, Aβ42 content, and expression levels of Tau proteins and phosphorylated Tau proteins in the brain.