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Volume 52 Issue 11
Nov.  2025
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Article Navigation >  Journal of Genetics and Genomics  > 2025  >  52(11): 1367-1375

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
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    a. Guangzhou Medical University, Guangzhou, Guangdong 511495, China;

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    b. Guangzhou National Laboratory, Guangzhou, Guangdong 510005, China;

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    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:

This work was supported in part by the National Key Basic Research and Development Program of China (2019YFA0801402, 2018YFA0107200, 2018YFA0801402, 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, 32100800).

  • Received Date: 2024-10-31
  • Accepted Date: 2025-02-17
  • Rev Recd Date: 2025-02-17
  • Publish Date: 2025-02-25
    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 with 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.
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