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TREM2 variants in Alzheimer's disease
Rita Guerreiro1, Aleksandra Wojtas, Jose Bras
1University College London (UCL) Institute of Neurology, London, United Kingdom.
The New England Journal of Medicine
|November 16, 2012
Summary
Rare variants in TREM2 increase Alzheimer's disease risk. This study found heterozygous TREM2 variants are significantly associated with developing Alzheimer's disease, highlighting TREM2's role in neurodegeneration.
Area of Science:
- Neurogenetics
- Molecular Biology
Background:
- Triggering receptor expressed on myeloid cells 2 (TREM2) mutations are linked to early-onset dementia.
- Understanding TREM2's role in Alzheimer's disease (AD) is crucial for developing new therapies.
Purpose of the Study:
- To investigate the association between TREM2 genetic variability and Alzheimer's disease risk.
- To analyze TREM2 expression patterns in the brain and in AD mouse models.
Main Methods:
- Genome, exome, and Sanger sequencing of 1092 AD patients and 1107 controls.
- Meta-analysis and genotyping of the TREM2 variant rs75932628 (R47H).
- Assay of TREM2 expression in human brain regions and differentially expressed genes in an AD mouse model.
Main Results:
- Increased TREM2 variants in AD patients compared to controls (P=0.02).
- The rs75932628 (R47H) variant showed highly significant association with AD (P<0.001).
- TREM2 expression differed between control and AD model mice.
Conclusions:
- Heterozygous rare variants in TREM2 significantly increase the risk of developing Alzheimer's disease.
- TREM2 is implicated as a key genetic factor in Alzheimer's disease pathogenesis.
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