近日，美国哥伦比亚大学教授Vilas Menon及其课题组发现了阿尔茨海默病的细胞类型特征在人群中共享。这一研究成果于2026年7月15日发表在国际顶尖学术期刊《自然》上。

为了弥补这一差距，小组对拉丁人、白人（不包括拉丁人）和非裔美国人（不包括拉丁人）的死后脑组织样本进行了单核RNA测序和转座酶可及染色质测序，以分析皮层和皮层下区域。通过对分子程序进行离散和连续的解剖，研究组以区域特异性的方式在所有三种人群中鉴定出与阿尔茨海默病相关的细胞类型特异性细胞，包括小胶质细胞（GPNMB⁺和CD74⁺亚组）、星形胶质细胞（SERPINH1⁺、CD44⁺和WIF1⁺亚组）和神经元（SST⁺ GABA能和浅层谷氨酸能）特征。

该团队还报道了星形胶质细胞和少突胶质细胞中的连续基因表达因子，这些因子没有被离散的细胞分配捕获，但它们与疾病表型有很强的相关性；这些因子富含与脂质加工和神经递质再摄取等注释功能相关的基因。最后，课题组研究人员发现分子程序揭示了跨越所有三个人群的认知障碍个体的六个不同亚组，这些亚组没有被神经病理学捕获，而是通过不普遍存在但仍与死前损伤相关的分子特征来区分。

总的来说，他们的研究确定了与阿尔茨海默病相关的关键细胞类型和基因程序，这些细胞类型和基因程序在人群中是共享的，并强调了代表性抽样如何能够捕获共享特征和疾病异质性，从而能够更好地确定关键细胞类型的优先级，以便进一步研究。

据了解，单细胞分辨率的基因组研究已经确定了几种与阿尔茨海默病的临床和病理特征相关的细胞类型，但尚未研究跨人群共有的关联。

附：英文原文

Title: Cell-type signatures of Alzheimer’s disease shared across population groups

Author: Luquez, Tain, Algoo, Jonathan, Chiu, Rebecca, Mares, Jason A., Yadav, Archana, Lam, Matti, Gaur, Pallavi, Lai, Xiaoying, Lee, Dylan I., Paryani, Fahad, Batchelor, Rafe, Belli, Irla, Henry, Jordan, Hoter-Ishay, Bat, Mattison, Courteney, Starr, Lindsey, Lama, Tsering, Karaahmet, Berke, Cao, Wenqing, De Jager, Philip L., Taga, Mariko, Barnes, Lisa L., Marquez, David X., Bennett, David A., Zhang, Ya, Menon, Vilas

Issue&Volume: 2026-07-15

Abstract: Genomic studies at single-cell resolution have identified several cell types associated with clinical and pathological traits in Alzheimer’s disease1,2,3,4,5,6,7,8,9, but have not examined associations that are shared across populations. To bridge this gap, here we use single-nucleus RNA sequencing and assay for transposase-accessible chromatin with sequencing to profile cortical and subcortical regions in post-mortem brain-tissue samples from Latin, white (excluding Latin) and African American (excluding Latin) individuals. Using discrete and continuous dissections of molecular programs, we identify cell-type-specific clusters associated with Alzheimer’s disease in a region-specific manner across all three population groups, including microglial (GPNMB+ and CD74+ subgroups), astrocytic (SERPINH1+, CD44+ and WIF1+ subgroups) and neuronal (SST+ GABAergic and superficial-layer glutamatergic) signatures. We also report continuous gene-expression factors in astrocytes and oligodendrocytes that are not captured by discrete cluster assignments, but which show strong associations with disease phenotypes; these factors are enriched for genes associated with annotated functions such as lipid processing and neurotransmitter reuptake. Finally, we find that molecular programs reveal six distinct subgroups of individuals with cognitive impairment that span all three populations, are not captured by neuropathology, and are instead distinguished by molecular signatures that are not universally present but are nonetheless associated with ante-mortem impairment. Overall, our study identifies key cell types and gene programs implicated in Alzheimer’s disease that are shared across population groups, and underscores how representative sampling can capture both shared signatures and disease heterogeneity, thereby enabling better prioritization of key cell types for further investigation.

DOI: 10.1038/s41586-026-10793-0

Source: https://www.nature.com/articles/s41586-026-10793-0