广州国家实验室景乃禾课题组开发出了淀粉样蛋白-β低聚物驱动非人类灵长类动物老年大脑中阿尔茨海默病的淀粉样沉积和级联tau病理。相关论文发表在2025年2月25日出版的《遗传学报》杂志上。

研究组将他们的研究扩展到中年食环猴（≤15岁）以建立AD模型。令人惊讶的是，免疫组织化学分析显示，即使在注射a β o后，中年猴子的大脑中也没有检测到ad相关的病理。在对38只猴子的综合病理分析中，该研究组观察到淀粉样蛋白-β (a β)负担随着年龄的增长而显著增加。值得注意的是，与老年猴子大脑的背侧区域相比，腹侧区域的β斑块密度明显更高。

此外，小组证明tau磷酸化与广泛的a β斑块的积累一致，并与老年猴子的a β负荷呈正相关。总的来说，这些发现强调了衰老的大脑在为a β o诱导的食蟹猴AD病理提供必要条件方面的关键作用。

研究人员表示，阿尔茨海默病（AD）是最常见的痴呆症，对老年人的影响尤为严重。虽然衰老被广泛认为是阿尔茨海默病的主要危险因素，但衰老导致阿尔茨海默病发病的确切机制尚不清楚。在他们之前的工作中，研究人员已经描述了老年食猴（≥18岁）脑实质注射淀粉样蛋白-β寡聚物（a -β o）后大脑的神经病理变化。

附：英文原文

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

Author: Wei Hong c, Su Feng b, Naihe Jing b

Issue&Volume: 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 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.

DOI: 10.1016/j.jgg.2025.02.007

Source: https://www.sciencedirect.com/science/article/abs/pii/S1673852725000529