ArticleAlzheimer's research & therapy2025
TREM2 risk variants and associated endophenotypes in alzheimer's disease.
Article in Alzheimer's research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed.
- An acetylated Tau-174 CSF biomarker discriminates between TDP-43 and tau pathology in patients with frontotemporal lobar degeneration.Nature medicine · 2026Article
- Current progress in pathway-targeted therapeutics for Alzheimer's disease: mechanistic insights and windows of opportunity.Molecular and cellular biochemistry · 2026Review
- Neurotransmitter Systems in Alzheimer's Disease.Current issues in molecular biology · 2026Review
- Phagocytes as plaque catalysts: Human macrophages generate seeding-competent Aβ42 fibrils with cross-seeding activity.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Protective PLCG2 variants associate with a delayed onset of Alzheimer's disease among heterozygous APOE ε4 carriers.Alzheimer's research & therapy · 2026Article
- TREM2 as a central hub of neuroimmune-metabolic crosstalk in central nervous system disorders: from microglial biology to therapeutic targeting.Frontiers in immunology · 2026Review
- Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025Review
- Phagocytes as Plaque Catalysts: Human Macrophages Actively Generate Pathogenic Aβ42 Fibrils with Seeding and Cross-Seeding Potency.bioRxiv : the preprint server for biology · 2025Article
- Is TREM2 a Stretch: Implications of TREM2 Along Spinal Cord Circuits in Health, Aging, Injury, and Disease.Cells · 2025Review
- 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
- Multiple sclerosis severity variant iniScience · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRare variants of the triggering receptor expressed on myeloid cell 2 (TREM2) gene are strong risk factors for Alzheimer's disease (AD), and drugs targeting the TREM2 protein are being developed. However, it is unknown what the effect of TREM2 variants is on the AD phenotype.
methodsHere we studied a full range of clinical and biomarker measures in a large cohort of TREM2 variant carriers (n = 123, 7.8%, i.e., R62H n = 66, R47H n = 26, T96K n = 16, other TREM2 variants n = 17) compared to confirmed non-carriers (n = 1,459) with biomarker confirmed symptomatic AD from Amsterdam Dementia Cohort. Secondly, we explored whether specific TREM2 variants were associated with distinct clinical measures compared to the reference group, i.e. non-carriers, within the same cohort.
resultsTREM2 variant carriers (64 ± 7 years, 54% female) did not show distinct clinical measures of AD at presentation compared to AD patients not carrying a TREM2 variant (64 ± 7 years, 52% female). We observed no differences in MMSE, neuropsychological domains (except less impaired visuospatial functioning in TREM2 carriers), MRI scores, CSF biomarkers, EEG, structural MRI (41 ROIs) and Tau-PET scans of four carriers (R62H, R47H, G58A, D87N). Carriers did show faster cognitive decline (MMSE points per year 0.6 ± 0.3, P
conclusionsThis study shows that while carriers of TREM2 risk variants cannot be distinguished based on clinical presentation at baseline compared to non-carriers, they do exhibit a faster global cognitive decline. Variant-specific analyses indicate that especially R47H and T96K carriers drive this association. These results highlight the importance of considering variant-specific effects for understanding the role of TREM2 biology in AD. The rich phenotype information can inform clinical stage drug development.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.