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Multi-cellular communities are perturbed in the aging human brain and with Alzheimer's disease

By Anael Cain, Mariko Taga, Cristin McCabe, Idan Hekselman, Charles C White, Gilad Green, Orit Rozenblatt-Rosen, Feng Zhang, Esti Yeger-Lotem, David A. Bennett, Hyun-Sik Yang, Aviv Regev, Vilas Menon, Naomi Habib, Phillip L. De Jager

Posted 23 Dec 2020
bioRxiv DOI: 10.1101/2020.12.22.424084

The role of different cell types and their interactions in Alzheimers disease (AD) is an open question that we have pursued by mapping the human brain at the single cell level. Here, we present a high resolution cellular map of the aging frontal cortex by single nucleus RNA-sequencing of 24 individuals with different clinicopathologic characteristics; which we used to infer the cellular architecture of 640 individuals from bulk RNA-seq profiles. Powered by this sample of sufficient size to obtain statistically robust results, we uncovered AD associations with neuronal subtypes and oligodendroglial states. Moreover, we uncovered a network of cellular communities, each composed of different neuronal, glial and endothelial cells subpopulations whose frequencies are correlated across individuals. Two of the cellular communities are altered in relation to cognitive decline and tau pathology. Our work provides a roadmap for evaluating cross-cell type differences in the cellular environment of the AD brain.

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