Amyloid-β oligomers drive amyloid deposit and cascaded tau pathology of Alzheimer&#39;s disease in aged brains of non-human primates

Zhengxiao He; Wenchang Zhang; Ping Chen; Siyao Li; Min Tao; Feng Yue; Wei Hong; Su Feng; Naihe Jing

doi:10.1016/j.jgg.2025.02.007

Amyloid-β oligomers drive amyloid deposit and cascaded tau pathology of Alzheimer's disease in aged brains of non-human primates

doi: 10.1016/j.jgg.2025.02.007

a. Guangzhou Medical University, Guangzhou, Guangdong 511495, China;
b. Guangzhou National Laboratory, Guangzhou, Guangdong 510005, China;
c. Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China;
d. State Key Laboratory of Digital Medical Engineering, School of Biomedical Engineering, Hainan University, Haikou, Hainan 570228, China

基金项目:

This work was supported in part by the National Key Basic Research and Development Program of China (2019YFA0801402, 2018YFA0107200, 2018YFA0801402, and 2018YFA0800100), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16020501 and XDA16020404), and the National Natural Science Foundation of China (32130030, 31900454, 32470866, 32471010, and 32100800). We are sincerely grateful to Dr. Dominic Walsh for his gift of antibodies.

详细信息

通讯作者:
Wei Hong,E-mail:wei.hong@siat.ac.cn

Su Feng,E-mail:feng_su@gzlab.ac.cn

Naihe Jing,E-mail:jing_naihe@gzlab.ac.cn

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出版历程
- 收稿日期: 2024-10-31
- 录用日期: 2025-02-17
- 修回日期: 2025-02-17
- 网络出版日期: 2025-07-11

Amyloid-β oligomers drive amyloid deposit and cascaded tau pathology of Alzheimer's disease in aged brains of non-human primates

Zhengxiao He^a,b,
Wenchang Zhang^b,
Ping Chen^c,
Siyao Li^c,
Min Tao^c,
Feng Yue^d,
Wei Hong^{c
, ,},
Su Feng^{b
, ,},
Naihe Jing^{b
, ,}

a. Guangzhou Medical University, Guangzhou, Guangdong 511495, China;
b. Guangzhou National Laboratory, Guangzhou, Guangdong 510005, China;
c. Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China;
d. State Key Laboratory of Digital Medical Engineering, School of Biomedical Engineering, Hainan University, Haikou, Hainan 570228, China

Funds:

摘要

摘要:
Alzheimer's disease (AD), the most prevalent form of dementia, disproportionately affects the elderly population. While aging is widely recognized as a major risk factor for AD, the precise mechanisms by which aging contributes to the pathogenesis of AD remain poorly understood. In our previous work, the neuropathological changes in the brains of aged cynomolgus monkeys (≥18 years old) following parenchymal cerebral injection of amyloid-β oligomers (AβOs) have been characterized. Here, we extend our investigation to middle-aged cynomolgus monkeys (≤15 years old) to establish an AD model. Surprisingly, immunohistochemical analysis reveals no detectable AD-related pathology in the brains of middle-aged monkeys, even after AβOs injection. In a comprehensive pathological analysis of 38 monkeys, we observe that the amyloid-β (Aβ) burden increases significantly with advancing age. Notably, the density of Aβ plaques is markedly higher in the ventral regions compared to the dorsal regions of aged monkey brains. Furthermore, we demonstrate that tau phosphorylation coincides with the accumulation of extensive Aβ plaques and exhibits a positive correlation with Aβ burden in aged monkeys. Collectively, these findings underscore the critical role of the aged brain in providing the necessary conditions for AβO-induced AD pathologies in cynomolgus monkeys.
- Alzheimer's disease /
- Aged brain /
- Amyloid-β oligomers /
- Non-human primate /
- Amyloid-β plaques /
- p-Tau
Abstract:
Alzheimer's disease (AD), the most prevalent form of dementia, disproportionately affects the elderly population. While aging is widely recognized as a major risk factor for AD, the precise mechanisms by which aging contributes to the pathogenesis of AD remain poorly understood. In our previous work, the neuropathological changes in the brains of aged cynomolgus monkeys (≥18 years old) following parenchymal cerebral injection of amyloid-β oligomers (AβOs) have been characterized. Here, we extend our investigation to middle-aged cynomolgus monkeys (≤15 years old) to establish an AD model. Surprisingly, immunohistochemical analysis reveals no detectable AD-related pathology in the brains of middle-aged monkeys, even after AβOs injection. In a comprehensive pathological analysis of 38 monkeys, we observe that the amyloid-β (Aβ) burden increases significantly with advancing age. Notably, the density of Aβ plaques is markedly higher in the ventral regions compared to the dorsal regions of aged monkey brains. Furthermore, we demonstrate that tau phosphorylation coincides with the accumulation of extensive Aβ plaques and exhibits a positive correlation with Aβ burden in aged monkeys. Collectively, these findings underscore the critical role of the aged brain in providing the necessary conditions for AβO-induced AD pathologies in cynomolgus monkeys.
- Alzheimer's disease /
- Aged brain /
- Amyloid-β oligomers /
- Non-human primate /
- Amyloid-β plaques /
- p-Tau

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Amyloid-β oligomers drive amyloid deposit and cascaded tau pathology of Alzheimer's disease in aged brains of non-human primates

doi: 10.1016/j.jgg.2025.02.007

通讯作者:
Wei Hong,E-mail:wei.hong@siat.ac.cn

Su Feng,E-mail:feng_su@gzlab.ac.cn

Naihe Jing,E-mail:jing_naihe@gzlab.ac.cn

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Amyloid-β oligomers drive amyloid deposit and cascaded tau pathology of Alzheimer's disease in aged brains of non-human primates

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Amyloid-β oligomers drive amyloid deposit and cascaded tau pathology of Alzheimer's disease in aged brains of non-human primates

doi: 10.1016/j.jgg.2025.02.007

通讯作者: Wei Hong,E-mail:wei.hong@siat.ac.cn Su Feng,E-mail:feng_su@gzlab.ac.cn Naihe Jing,E-mail:jing_naihe@gzlab.ac.cn

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Amyloid-β oligomers drive amyloid deposit and cascaded tau pathology of Alzheimer's disease in aged brains of non-human primates

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出版历程

目录

通讯作者:
Wei Hong,E-mail:wei.hong@siat.ac.cn

Su Feng,E-mail:feng_su@gzlab.ac.cn

Naihe Jing,E-mail:jing_naihe@gzlab.ac.cn