Integrated phenotypic and proteomic screening identifies top-tier Alzheimer's disease therapeutic targets.

ABSTRACT:

Introduction

Alzheimer's disease (AD) is a complex neurodegenerative disorder. Hundreds of therapeutic targets have been nominated through genetic and multi-omic studies, but effective prioritization remains a major bottleneck.

Methods

We applied an integrative screening framework to assess 29 candidate targets from risk-enriched biological domains. Using disease-relevant murine BV2 microglial cell lines with stable Psen2 knockdown, we performed siRNA-mediated perturbations followed by cellular phenotypic assays and quantitative proteomics.

Results

Twenty-five candidate targets significantly altered at least one phenotype, with stronger effects in Psen2 knockdown cells. Integrated proteomic analyses identified several perturbations that reversed AD-associated molecula

SUBMITTER: Cary GA 

PROVIDER: S-EPMC12632979 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature