Laboratory Animal and Comparative Medicine, Volume. 45, Issue 3, 269(2025)

Establishment of a Rat Model of Alzheimer's Disease by Introducing Human Triple Mutant APP Gene into Hippocampus via Brain Stereotactic Technology

XIAO Linlin1,2, YANG Yixuan1,2, LI Shanshan1,2, LUO Lanshiyu1,2, YIN Siwei1,2, SUN Juming1, SHI Wei1, OUYANG Yiqiang1, and LI Xiyi3、*
Author Affiliations
  • 1Laboratory Animal Center, Guangxi Medical University, Nanning 530021, China
  • 2School of Basic Medical Sciences, Guangxi Medical University, Nanning 530021, China
  • 3School of Public Health, Guangxi Medical University, Nanning 530021, China
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    ObjectiveTo establish a rat model of Alzheimer's disease (AD) expressing human triple mutant amyloid precursor protein (APP) in the hippocampus, and to provide a model for the study of disease mechanisms and drug development.MethodsTwenty-four 12-week-old SPF-grade female SD rats were randomly divided into a blank control group, a virus control group and an experimental group, with eight rats in each group; among them, the experimental group received a stereotaxic injection of adeno-associated virus (AAV) carrying the human triple mutant APP and NanoLuc luciferase genes into the hippocampus. In vivo imaging was used to observe viral expression in the brains of rats in each group, the novel object recognition test was used to assess the recognition memory of the rats in each group, real-time fluorescent quantitative PCR was used to detect the expression level of the APP gene, HE staining was used to examine the brain histopathology, Nissl staining was used to assess the hippocampal lesions, and immunohistochemistry was used to detect the deposition of amyloid β-protein (Aβ).ResultsIn vivo imaging showed that reporter fluorescence was detected in the brains of rats in both experimental and virus control groups. Fluorescence quantitative PCR showed that the expression level of the APP gene was significantly increased in the brains of rats in the experimental group (P<0.01). Novel object recognition test revealed that the recognition memory of rats in the experimental group was significantly reduced compared with that of the blank control group (P<0.01). Six months after recombinant AAV virus infection, HE staining and Nissl staining of brain tissues showed that the number of neurons and Nissl bodies in the CA1 region of the hippocampus in the experimental group was reduced and disorganized; immunohistochemistry testing of the CA1 region of the hippocampus and the pyramidal cell layer of the experimental group revealed prominent brown deposits, indicating Aβ protein deposition.ConclusionThe rat model successfully established by stereotaxic injection and AAV-mediated delivery of human triple mutant APP gene exhibits typical AD features, providing a valuable animal model for studying AD pathology and developing drug therapies targeting Aβ protein deposition.

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    XIAO Linlin, YANG Yixuan, LI Shanshan, LUO Lanshiyu, YIN Siwei, SUN Juming, SHI Wei, OUYANG Yiqiang, LI Xiyi. Establishment of a Rat Model of Alzheimer's Disease by Introducing Human Triple Mutant APP Gene into Hippocampus via Brain Stereotactic Technology[J]. Laboratory Animal and Comparative Medicine, 2025, 45(3): 269

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    Paper Information

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    Received: Mar. 1, 2025

    Accepted: Aug. 26, 2025

    Published Online: Aug. 26, 2025

    The Author Email: LI Xiyi (leeciyee@163.com)

    DOI:10.12300/j.issn.1674-5817.2025.030

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