Cellular communities reveal trajectories of brain ageing and Alzheimer's disease.

ABSTRACT: Alzheimer's disease (AD) has recently been associated with diverse cell states^1-11, yet when and how these states affect the onset of AD remains unclear. Here we used a data-driven approach to reconstruct the dynamics of the brain's cellular environment and identified a trajectory leading to AD that is distinct from other ageing-related effects. First, we built a comprehensive cell atlas of the aged prefrontal cortex from 1.65 million single-nucleus RNA-sequencing profiles sampled from 437 older individuals, and identified specific glial and neuronal subpopulations associated with AD-related traits. Causal modelling then prioritized two distinct lipid-associated microglial subpopulations-one drives amyloid-β proteinopathy while the other mediates the effect of amyloid-β on tau p

SUBMITTER: Green GS 

PROVIDER: S-EPMC11877878 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature