AI Article Synopsis
- * The study utilized a variety of genetic analysis methods on large patient cohorts, confirming that p.R47H is associated with earlier symptom onset in AD patients but does not influence frontotemporal dementia or Creutzfeldt-Jakob disease.
- * Overall, the findings emphasize that while p.R47H is linked to increased risk for AD, it does not affect other neurodegenerative disorders studied.
Article Abstract
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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627504 | PMC |
| http://dx.doi.org/10.1016/j.jalz.2014.05.1751 | DOI Listing |
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