Paper
Document
Submit new version
Download
Flag content
Preprint
14

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

14
TipTip
Save
Document
Submit new version
Download
Flag content

Abstract

Abstract The role of different cell types and their interactions in Alzheimer’s disease (AD) is an open question. Here we pursued it by assembling a high-resolution cellular map of the aging frontal cortex by single nucleus RNA-seq of 24 individuals with different clinicopathologic characteristics. We used the map to infer the neocortical cellular architecture of 638 individuals profiled by bulk RNA-seq, providing the sample size necessary for identifying statistically robust associations. We uncovered diverse cell populations associated with AD, including inhibitory neuronal subtypes and oligodendroglial states. We further recovered a network of multicellular communities, each composed of coordinated subpopulations of neuronal, glial and endothelial cells, and found that two of these communities are altered in AD. Finally, we used mediation analyses to prioritize cellular changes that might contribute to cognitive decline. Thus, our deconstruction of the aging neocortex provides a roadmap for evaluating the cellular microenvironments underlying AD and dementia.

Paper PDF

Empty State
This PDF hasn't been uploaded yet.
Do not upload any copyrighted content to the site, only open-access content.
or