Last reviewed: June 1, 2026

2019Cell Reports

The major risk factors for Alzheimer's disease: age, sex, and genes modulate the microglia response to Abeta plaques

Sala Frigerio C, Wolfs L, Fattorelli N, Thrupp N, Voytyuk I, Schmidt I, et al.

Abstract summary

Single-cell RNA-seq of human AD and control brains revealed microglial heterogeneity modulated by age, sex, and TREM2/APOE genotype. Identified human microglial sub-states not present in mouse models, including a population characterized by high MHC-II expression. Demonstrated that genetic risk factors directly shape microglial transcriptional states.

Evidence labels

single-cell RNA-seqhuman tissue

Targets

Diseases

  • Alzheimer's disease

Species

human

Methods

single-cell RNA-seq, immunohistochemistry

Therapeutic relevance

Reveals sex- and age-dependent microglial states that may explain variable treatment responses and inform precision medicine in AD.

Last reviewed: June 1, 2026