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

ABSTRACT:

Background

A significant proportion of individuals maintain healthy cognitive function despite having extensive Alzheimer's disease (AD) pathology, known as cognitive resilience. Understanding the molecular mechanisms that protect these individuals can identify therapeutic targets for AD dementia. This study aims to define molecular and cellular signatures of cognitive resilience, protection and resistance, by integrating genetics, bulk RNA, and single-nucleus RNA sequencing data across multiple brain regions from AD, resilient, and control individuals.

Methods

We analyzed data from the Religious Order Study and the Rush Memory and Aging Project (ROSMAP), including bulk (n=631) and multi-regional single nucleus (n=48) RNA sequencing. Subjects were categorized into AD, resili

SUBMITTER: Castanho I 

PROVIDER: S-EPMC11761133 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature