ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
The TREM2 H157Y variant is associated with more severe neurodegeneration in Alzheimer's disease and altered immune-related processes.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Small-Molecule NANT Therapeutics Targeting the Brain-Immune Axis in Alzheimer's Disease: Mechanisms, Clinical Progress, and Translational Challenges.Molecules (Basel, Switzerland) · 2026Review
- Could the cognitive benefits of amyloid-beta clearance grow in time for Alzheimer's disease?Translational psychiatry · 2026Review
- Head-to-head comparison of brain-derived pTau217 and total pTau217 for brain amyloid and tau pathology classification.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- TREM2-directed therapy in Alzheimer's disease: from therapeutic window to clinical translation.Frontiers in aging neuroscience · 2026Review
- TREM2 as a central hub of neuroimmune-metabolic crosstalk in central nervous system disorders: from microglial biology to therapeutic targeting.Frontiers in immunology · 2026Review
- The TREM2 H157Y variant is associated with more severe neurodegeneration in Alzheimer's disease and altered immune-related processes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Unmasking early microglial remodeling in an Alzheimer's disease mouse model.Frontiers in cellular neuroscience · 2025Article
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Authors and funding
12 authors.
Funding
Abstract
introductionMultiple TREM2 variants are associated with an increased risk of Alzheimer's disease (AD). TREM2 H157Y is the only variant located at the proteolytic cleavage site that enhances TREM2 protein shedding. While this variant is associated with increased AD risk predominantly in the Chinese population, its impact on AD pathology is largely unknown.
methodsWe conducted an in-depth study integrating clinical cases, neuroimaging data, and blood proteomic data.
resultsTREM2 H157Y variant carriers with AD exhibit more severe AD pathology, more severe neurodegeneration, and more rapid clinical progression. Cognitively normal individuals carrying the variant show changes in blood proteins that are associated with neurodegeneration and inflammation. Moreover, the TREM2 H157Y variant is associated with altered immune and vascular processes irrespective of disease state. DISCUSSION: These findings highlight the clinical implications of the TREM2 H157Y variant and the use of blood proteomic data to investigate the effects of genetic variants on disease-related endophenotypes. HIGHLIGHTS: The TREM2 H157Y variant is associated with more rapid clinical progression of Alzheimer's disease only in the presence of the apolipoprotein E (APOE) ε4 allele. The TREM2 H157Y variant is associated with neurodegeneration, irrespective of disease state. The TREM2 H157Y variant is associated with altered immune and vascular processes, irrespective of disease state. Cognitively normal TREM2 H157Y carriers show altered disease-associated blood proteins related to peripheral immune response. Blood proteomic data can be used to study the impacts of disease-associated genetic variants on disease outcomes and biological processes involved in pathogenesis.
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