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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2024

Open Access 01-12-2024 | Alzheimer's Disease | Research

A nonhuman primate model with Alzheimer’s disease-like pathology induced by hippocampal overexpression of human tau

Authors: Zhouquan Jiang, Jing Wang, Yongpeng Qin, Shanggong Liu, Bin Luo, Fan Bai, Huiyi Wei, Shaojuan Zhang, Junjie Wei, Guoyu Ding, Long Ma, Shu He, Rongjie Chen, Ying Sun, Yi Chen, Lu Wang, Hao Xu, Xiangyu Wang, Gong Chen, Wenliang Lei

Published in: Alzheimer's Research & Therapy | Issue 1/2024

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Abstract

Background

Alzheimer’s disease (AD) is one of the most burdening diseases of the century with no disease-modifying treatment at this time. Nonhuman primates (NHPs) share genetic, anatomical, and physiological similarities with humans, making them ideal model animals for investigating the pathogenesis of AD and potential therapies. However, the use of NHPs in AD research has been hindered by the paucity of AD monkey models due to their long generation time, ethical considerations, and technical challenges in genetically modifying monkeys.

Methods

Here, we developed an AD-like NHP model by overexpressing human tau in the bilateral hippocampi of adult rhesus macaque monkeys. We evaluated the pathological features of these monkeys with immunostaining, Nissl staining, cerebrospinal fluid (CSF) analysis, magnetic resonance imaging (MRI), positron emission tomography (PET), and behavioural tests.

Results

We demonstrated that after hippocampal overexpression of tau protein, these monkeys displayed multiple pathological features of AD, including 3-repeat (3R)/4-repeat (4R) tau accumulation, tau hyperphosphorylation, tau propagation, neuronal loss, hippocampal atrophy, neuroinflammation, Aβ clearance deficits, blood vessel damage, and cognitive decline. More interestingly, the accumulation of both 3R and 4R tau is specific to NHPs but not found in adult rodents.

Conclusions

This work establishes a tau-induced AD-like NHP model with many key pathological and behavioural features of AD. In addition, our model may potentially become one of the AD NHP models adopted by researchers worldwide since it can be generated within 2 ~ 3 months through a single injection of AAVs into the monkey brains. Hence, our model NHPs may facilitate mechanistic studies and therapeutic treatments for AD.
Appendix
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Metadata
Title
A nonhuman primate model with Alzheimer’s disease-like pathology induced by hippocampal overexpression of human tau
Authors
Zhouquan Jiang
Jing Wang
Yongpeng Qin
Shanggong Liu
Bin Luo
Fan Bai
Huiyi Wei
Shaojuan Zhang
Junjie Wei
Guoyu Ding
Long Ma
Shu He
Rongjie Chen
Ying Sun
Yi Chen
Lu Wang
Hao Xu
Xiangyu Wang
Gong Chen
Wenliang Lei
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2024
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-024-01392-0

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