Cell · 2023
Single-cell atlas reveals correlates of high cognitive function, dementia, and resilience to Alzheimer's disease pathology.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Mathys Hansruedi, Peng Zhuyu, Boix Carles A, Victor Matheus B, Leary Noelle, Babu Sudhagar, Abdelhady Ghada, Jiang Xueqiao, Ng Ayesha P, Ghafari Kimia, Kunisky Alexander K, Mantero Julio, Galani Kyriaki, Lohia Vanshika N, Fortier Gabrielle E, Lotfi Yasmine, Ivey Jason, Brown Hannah P, Patel Pratham R, Chakraborty Nehal, Beaudway Jacob I, Imhoff Elizabeth J, Keeler Cameron F, McChesney Maren M, Patel Haishal H, Patel Sahil P, Thai Megan T, Bennett David A, Kellis Manolis, Tsai Li-Huei
Аннотация
Alzheimer's disease (AD) is the most common cause of dementia worldwide, but the molecular and cellular mechanisms underlying cognitive impairment remain poorly understood. To address this, we generated a single-cell transcriptomic atlas of the aged human prefrontal cortex covering 2.3 million cells from postmortem human brain samples of 427 individuals with varying degrees of AD pathology and cognitive impairment. Our analyses identified AD-pathology-associated alterations shared between excitatory neuron subtypes, revealed a coordinated increase of the cohesin complex and DNA damage response factors in excitatory neurons and in oligodendrocytes, and uncovered genes and pathways associated with high cognitive function, dementia, and resilience to AD pathology. Furthermore, we identified selectively vulnerable somatostatin inhibitory neuron subtypes depleted in AD, discovered two distinct groups of inhibitory neurons that were more abundant in individuals with preserved high cognitive function late in life, and uncovered a link between inhibitory neurons and resilience to AD pathology.