The gain-of-function TREM2-T96K mutation increases risk for Alzheimer's disease by impairing microglial function.

doi:10.1016/j.neuron.2025.09.032

Loading publication...

Noodle always counts identifier-free feature events for service operation. With your permission, Google Analytics can also estimate audience and engagement. Search text, publication identifiers, cookies, IP addresses and browser fingerprints are never included in Noodle's first-party event counters.

Privacy details

Community

Back to search

Article

The gain-of-function TREM2-T96K mutation increases risk for Alzheimer's disease by impairing microglial function.

Neuron - 7 Jan 2026

Pilat Dominika J, Le Hoang, Prokopenko Dmitry, Lin Chih-Chung Jerry, Eimer William A, Quinti Luisa, Gavrilles Evan P, Garcia Sheyla N, Heitman Sara N, McGinty Danielle, Cetinbas Murat, Sadreyev Ruslan I, Tanzi Rudolph E, Griciuc Ana

Abstract excerpt

We previously reported that T96K is a gain-of-function mutation in TREM2 based on its ability to increase ligand-dependent activation. Here, we show that TREM2T96K increases risk for Alzheimer's disease (AD) in a whole-genome sequencing dataset comprised of family-based and case-control samples. Trem2T96K also reduced clustering of microglia around β-amyloid (Aβ) plaques exclusively in female 5xFAD mice....

Read the complete abstract on PubMed

Topics

Microglia
Alzheimer Disease
Animals
Membrane Glycoproteins
Receptors, Immunologic

Methodology Data sources Editorial policy Privacy Delete account & data About Contact Helena Bioinformatics

Humans

Female

Mice

Male

Mice, Transgenic

Gain of Function Mutation

Amyloid beta-Peptides

Plaque, Amyloid

Genetic Predisposition to Disease

Source

Open in PubMed Open full text

Identifiers

PMID: 41109213
DOI: 10.1016/j.neuron.2025.09.032
PMCID: PMC12687738

Genes

TREM2
STAT3

Variants

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 23 Oct 2026.

Related research

Semantic proximity does not establish scientific evidence. Graph snapshot: 2026-09-29.

Research trail→

Click a neighbor to travelStep 1 · 12 closest

The gain-of-function TREM2-T96K mutation increases risk for Alzheimer's disease by impairing microglial function.PMID 41109213Read ↗

TREM2 variants: new keys to decipher Alzheimer disease pathogenesis.Semantic proximity Read ↗

Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H polymorphism.Semantic proximity Read ↗

TREM2 lipid sensing sustains the microglial response in an Alzheimer's disease model.Semantic proximity Read ↗

AD-linked R47H- TREM2 mutation induces disease-enhancing proinflammatory microglial states in mice and humansSemantic proximity Read ↗

TREM2 Alzheimer's variant R47H causes similar transcriptional dysregulation to knockout, yet only subtle functional phenotypes in human iPSC-derived macrophages.Semantic proximity Read ↗

Gene expression and functional deficits underlie TREM2-knockout microglia responses in human models of Alzheimer's disease.Semantic proximity Read ↗

Trem2 R47H mutation shows mild, but functionally divergent alterations in microglial phenotypes compared to Trem2 deficiency in aged AppNL-F knock-in mice.Semantic proximity Read ↗

The role of TREM2 in Alzheimer's disease and other neurodegenerative disorders.Semantic proximity Read ↗

Trem2 R47H mutation shows mild, but functionally divergent alterations in microglial phenotypes compared to Trem2 deficiency in aged App NL-F knock-in miceSemantic proximity Read ↗

Shifting paradigms: The central role of microglia in Alzheimer's disease.Semantic proximity Read ↗

R47H Variant of TREM2 Associated With Alzheimer Disease in a Large Late-Onset Family: Clinical, Genetic, and Neuropathological Study.Semantic proximity Read ↗

Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditionsSemantic proximity Read ↗

⌁Select a neighboring publication to make it the new centre.