Person: Gao, Fan
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Publication Single-Cell Transcriptomic Analysis of Alzheimer’s Disease(Springer Science and Business Media LLC, 2019-05-01) Gao, Fan; Kellis, Manolis; Mathys, Hansruedi; Davila-Velderrain, Jose; Peng, Zhuyu; Mohammadi, Shahin; Young, Jennie; Menon, Madhvi; He, Liang; Abdurrob, Fatema; Jiang, Xueqiao; Martorell, Anthony; Ransohoff, Richard; Hafler, Brian; Bennett, David; Tsai, Li-HueiAlzheimer’s disease (AD) is a pervasive neurodegenerative disorder whose molecular and cellular complexity remains poorly understood. Here, we profiled and analyzed 80,660 single-nucleus transcriptomes from prefrontal cortex of 48 individuals with varying degrees of AD pathology. We identified transcriptionally-distinct subpopulations across six major brain cell-types, including those associated with pathology and characterized by regulators of myelination, inflammation, and neuron survival. The strongest AD-associated changes appeared early in pathological progression and were highly cell type-specific, whereas genes upregulated in late-stage were common across cell types and primarily involved in global stress response. Surprisingly, we found an overrepresentation of female cells in AD-associated subpopulations, and substantially different transcriptional responses between sexes in multiple cell types including oligodendrocytes. Overall, myelination-related processes were recurrently perturbed in multiple cell types, suggesting a key role in AD pathophysiology. Our single-cell transcriptomic resource provides a first blueprint for interrogating the molecular underpinnings and cellular basis of AD.