Grey matter ageing-related tau astrogliopathy (ARTAG) pathology is common in aged brains and detected in multiple brain regions. However, the associations of grey matter ARTAG with Alzheimer's disease and other common age-related proteinopathies, in addition to clinical phenotypes, including Alzheimer's dementia and cognitive decline, remain unclear. We examined 442 decedents (mean age at death = 90 years, males = 32%) from three longitudinal community-based clinical–pathological studies. Using AT8 immunohistochemistry, grey matter ARTAG pathology was counted in the superior frontal region, anterior temporal tip and amygdala and summarized as a severity score ranging from zero (none) to six (severe). Alzheimer's disease and other common age-related neuropathologies were also evaluated. The diagnosis of Alzheimer's dementia was based on clinical evaluations; annual tests of cognitive performance were summarized as global cognition and five cognitive domains. Multivariable logistic regression tested the associations of grey matter ARTAG pathology with an array of age-related neuropathologies. To evaluate associations of grey matter ARTAG pathology with Alzheimer's dementia and cognitive decline, we used logistic regression and linear mixed-effect models. Grey matter ARTAG pathology was seen in 324 (73%) participants, of which 303 (68%) participants had ARTAG in the amygdala, 246 (56%) in the anterior temporal tip and 137 (31%) in the superior frontal region. Grey matter ARTAG pathology from each of the three regions was associated with a pathological diagnosis of Alzheimer's disease and limbic-predominant age-related TAR DNA-binding protein 43 encephalopathy–neuropathological change but not with vascular pathology. In fully adjusted models that controlled for demographics, Alzheimer's disease and common age-related pathologies, an increase in severity of grey matter ARTAG pathology in the superior frontal cortex, but not in the amygdala or the anterior temporal tip, was associated with higher odds of Alzheimer's dementia and faster decline in global cognition, episodic memory and semantic memory. These results provide compelling evidence that grey matter ARTAG, specifically in the superior frontal cortex, contributes to Alzheimer's dementia and cognitive decline in old age.

中文翻译：

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灰质衰老相关的 tau 星形胶质细胞病：与脑部病变和认知能力下降的相关性


灰质衰老相关的 tau 星形胶质细胞病 （ARTAG） 病理在老年大脑中很常见，并在多个大脑区域检测到。然而，灰质ARTAG与阿尔茨海默病和其他常见的年龄相关蛋白质病的关联，以及临床表型，包括阿尔茨海默病痴呆和认知能力下降，仍不清楚。我们检查了来自三项基于社区的纵向临床病理学研究的 442 名死者 （平均死亡年龄 = 90 岁，男性 = 32%）。使用 AT8 免疫组化，在额上区、颞叶前尖端和杏仁核计数灰质 ARTAG 病理，并总结为从 0 （无） 到 6 （严重） 的严重程度评分。还评估了阿尔茨海默病和其他常见的与年龄相关的神经病理学。阿尔茨海默病痴呆的诊断基于临床评估;认知表现的年度测试总结为整体认知和 5 个认知领域。多变量 logistic 回归检验了灰质 ARTAG 病理与一系列与年龄相关的神经病理学的关联。为了评估灰质 ARTAG 病理与阿尔茨海默病痴呆和认知能力下降的关联，我们使用了 logistic 回归和线性混合效应模型。在 324 名 （73%） 参与者中观察到灰质 ARTAG 病理，其中 303 名 （68%） 参与者在杏仁核中患有 ARTAG，246 名 （56%） 在颞前尖端，137 名 （31%） 在额上区。来自三个区域的灰质 ARTAG 病理与阿尔茨海默病和边缘病为主的年龄相关 TAR DNA 结合蛋白 43 脑病神经病理变化相关，但与血管病理无关。 在控制人口统计学、阿尔茨海默病和常见年龄相关病症的完全调整模型中，额叶上皮层灰质 ARTAG 病理严重程度的增加，但不在杏仁核或颞叶前尖端，与阿尔茨海默病痴呆的较高几率和整体认知、情景记忆和语义记忆的更快下降有关。这些结果提供了令人信服的证据，表明灰质 ARTAG，特别是在额叶上皮层，导致老年阿尔茨海默氏症痴呆和认知能力下降。