R47H TREM2 variant increases risk of typical early‐onset Alzheimer's disease but not of prion or frontotemporal dementia. Issue 6 (23rd August 2014)

• Record Type: Journal Article
• Authors: Slattery, Catherine F.; Beck, Jonathan A.; Harper, Lorna; Adamson, Gary; Abdi, Zeinab; Uphill, James; Campbell, Tracy; Druyeh, Ron; Mahoney, Colin J.; Rohrer, Jonathan D.; Kenny, Janna; Lowe, Jessica; Leung, Kelvin K.; Barnes, Josephine; Clegg, Shona L.; Blair, Melanie; Nicholas, Jennifer M.; Guerreiro, Rita J.; Rowe, James B.; Ponto, Claudia; Zerr, Inga; Kretzschmar, Hans; Gambetti, Pierluigi; Crutch, Sebastian J.; Warren, Jason D.; Rossor, Martin N.; Fox, Nick C.; Collinge, John; Schott, Jonathan M.; Mead, Simon
• Is Part Of: Alzheimer's & dementia. Volume 10:Issue 6(2014)
• Page Start: 602
• Page End: 608.e4
• Publication Date: 2014-08-23
• Subjects: TREM2 -- Alzheimer's -- Frontotemporal dementia -- Prion -- Phenotype; Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1016/j.jalz.2014.05.1751
• Languages: English
• ISSNs: 1552-5260

Abstract

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.