Frequency of the TREM2 R47H Variant in Various Neurodegenerative Disorders

Area of Science:

• Neurogenetics
• Neurodegenerative Diseases
• Alzheimer Disease Research

Background:

• The TREM2 p.R47H variant (rs75932628) is a known risk factor for Alzheimer disease (AD).
• Evidence linking this variant to other neurodegenerative diseases is inconsistent.
• Understanding the specific associations of TREM2 variants is crucial for disease mechanisms.

Purpose of the Study:

• To investigate the frequency of the TREM2 R47H variant in a large, diverse cohort of patients with various neurodegenerative diseases.
• To clarify the association of the R47H variant with Alzheimer disease and other neurodegenerative conditions.

Main Methods:

• A multicenter cohort study involving 3058 patients diagnosed with Alzheimer disease, frontotemporal dementia spectrum syndromes, mild cognitive impairment, progressive supranuclear palsy syndrome, corticobasal syndrome, or amyotrophic lateral sclerosis.
• Genotyping for the TREM2 R47H variant was performed.
• Comparison of variant frequency between patient groups and 5089 control subjects.

Main Results:

• A statistically significant association was observed between the TREM2 R47H variant and Alzheimer disease.
• No significant association was found between the R47H variant and frontotemporal dementia spectrum syndromes, mild cognitive impairment, progressive supranuclear palsy syndrome, corticobasal syndrome, or amyotrophic lateral sclerosis.

Conclusions:

• The findings confirm the robust association between the TREM2 R47H variant and an increased risk of Alzheimer disease.
• This study provides no evidence to support a link between the TREM2 R47H variant and other investigated neurodegenerative diseases.