R47H TREM2 variant increases risk of typical early‐onset Alzheimer's disease but not of prion or frontotemporal dementia
CF Slattery, JA Beck, L Harper… - Alzheimer's & …, 2014 - Wiley Online Library
CF Slattery, JA Beck, L Harper, G Adamson, Z Abdi, J Uphill, T Campbell, R Druyeh…
Alzheimer's & dementia, 2014•Wiley Online LibraryBackground Rare TREM2 variants are significant risk factors for Alzheimer's disease (AD).
Methods We used next generation sequencing of the whole gene (n= 700), exon 2 Sanger
sequencing (n= 2634), p. R47H genotyping (n= 3518), and genome wide association study
imputation (n= 13,048) to determine whether TREM2 variants are risk factors or phenotypic
modifiers in patients with AD (n= 1002), frontotemporal dementia (n= 358), sporadic (n=
2500), and variant (n= 115) Creutzfeldt‐Jakob disease (CJD). Results We confirm only p …
Methods We used next generation sequencing of the whole gene (n= 700), exon 2 Sanger
sequencing (n= 2634), p. R47H genotyping (n= 3518), and genome wide association study
imputation (n= 13,048) to determine whether TREM2 variants are risk factors or phenotypic
modifiers in patients with AD (n= 1002), frontotemporal dementia (n= 358), sporadic (n=
2500), and variant (n= 115) Creutzfeldt‐Jakob disease (CJD). Results We confirm only p …
Background
Rare TREM2 variants are significant risk factors for Alzheimer's disease (AD).
Methods
We used next generation sequencing of the whole gene (n = 700), exon 2 Sanger sequencing (n = 2634), p.R47H genotyping (n = 3518), and genome wide association study imputation (n = 13,048) to determine whether TREM2 variants are risk factors or phenotypic modifiers in patients with AD (n = 1002), frontotemporal dementia (n = 358), sporadic (n = 2500), and variant (n = 115) Creutzfeldt‐Jakob disease (CJD).
Results
We confirm only p.R47H as a risk factor for AD (odds ratio or OR = 2.19; 95% confidence interval or CI = 1.04‐4.51; P = .03). p.R47H does not significantly alter risk for frontotemporal dementia (OR = 0.81), variant or sporadic CJD (OR = 1.06 95%CI = 0.66‐1.69) in our cohorts. Individuals with p.R47H associated AD (n = 12) had significantly earlier symptom onset than individuals with no TREM2 variants (n = 551) (55.2 years vs. 61.7 years, P = .02). We note that heterozygous p.R47H AD is memory led and otherwise indistinguishable from “typical” sporadic AD.
Conclusion
We find p.R47H is a risk factor for AD, but not frontotemporal dementia or prion disease.
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