衰老
小胶质细胞
神经退行性变
炎症
神经科学
阿尔茨海默病
认知功能衰退
神经炎症
氧化应激
疾病
医学
神经胶质
衰老的大脑
脑老化
病理
生物
免疫学
痴呆
中枢神经系统
内科学
作者
Victor Lau,Leanne M. Ramer,Marie‐Ève Tremblay
标识
DOI:10.1038/s41467-023-37304-3
摘要
Alzheimer's disease (AD) predominantly occurs as a late onset (LOAD) form involving neurodegeneration and cognitive decline with progressive memory loss. Risk factors that include aging promote accumulation of AD pathologies, such as amyloid-beta and tau aggregates, as well as inflammation and oxidative stress. Homeostatic glial states regulate and suppress pathology buildup; inflammatory states exacerbate pathology by releasing pro-inflammatory cytokines. Multiple stresses likely induce glial senescence, which could decrease supportive functions and reinforce inflammation. In this perspective, we hypothesize that aging first drives AD pathology burden, whereafter AD pathology putatively induces glial senescence in LOAD. We hypothesize that increasing glial senescence, particularly local senescent microglia accumulation, sustains and drives perpetuating buildup and spread of AD pathologies, glial aging, and further senescence. We predict that increasing glial senescence, particularly local senescent microglia accumulation, also transitions individuals from healthy cognition into mild cognitive impairment and LOAD diagnosis. These pathophysiological underpinnings may centrally contribute to LOAD onset, but require further mechanistic investigation.
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