Molecular hallmarks of excitatory and inhibitory neuronal resilience to Alzheimer's disease.

ABSTRACT:

Background

A significant proportion of individuals maintain cognition despite extensive Alzheimer's disease (AD) pathology, known as cognitive resilience. Understanding the molecular mechanisms that protect these individuals could reveal therapeutic targets for AD.

Methods

This study defines molecular and cellular signatures of cognitive resilience by integrating bulk RNA and single-cell transcriptomic data with genetics across multiple brain regions. We analyzed data from the Religious Order Study and the Rush Memory and Aging Project (ROSMAP), including bulk RNA sequencing (n = 631 individuals) and multiregional single-nucleus RNA sequencing (n = 48 individuals). Subjects were categorized into AD, resilient, and control based on β-amyloid and tau pathology, and cognitive s

SUBMITTER: Castanho I 

PROVIDER: S-EPMC12487324 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature