Details

Autor(en) / Beteiligte

• 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

Titel

R47H TREM2 variant increases risk of typical early-onset Alzheimer's disease but not of prion or frontotemporal dementia

Ist Teil von

• Alzheimer's & dementia, 2014-11, Vol.10 (6), p.602-608.e4

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.