Title: Investigating the role of rare heterozygous TREM2 variants in Alzheimer's disease and frontotemporal dementia
Authors: Cuyvers, Elise ×
Bettens, Karolien
Philtjens, Stéphanie
Van Langenhove, Tim
Gijselinck, Ilse
van der Zee, Julie
Engelborghs, Sebastiaan
Vandenbulcke, Mathieu
Van Dongen, Jasper
Geerts, Nathalie
Maes, Githa
Mattheijssens, Maria
Peeters, Karin
Cras, Patrick
Vandenberghe, Rik
De Deyn, Peter P
Van Broeckhoven, Christine
Cruts, Marc
Sleegers, Kristel
BELNEU consortium #
Issue Date: Oct-2014
Publisher: Elsevier
Series Title: Neurobiology of Aging vol:35 issue:3
Article number: 726.e11
Abstract: Homozygous mutations in exon 2 of TREM2, a gene involved in Nasu-Hakola disease, can cause frontotemporal dementia (FTD). Moreover, a rare TREM2 exon 2 variant (p.R47H) was reported to increase the risk of Alzheimer's disease (AD) with an odds ratio as strong as that for APOEε4. We systematically screened the TREM2 coding region within a Belgian study on neurodegenerative brain diseases (1216 AD patients, 357 FTD patients, and 1094 controls). We observed an enrichment of rare variants across TREM2 in both AD and FTD patients compared to controls, most notably in the extracellular IgV-set domain (relative risk = 3.84 [95% confidence interval = 1.29-11.44]; p = 0.009 for AD; relative risk = 6.19 [95% confidence interval = 1.86-20.61]; p = 0.0007 for FTD). None of the rare variants individually reached significant association, but the frequency of p.R47H was increased ∼3-fold in both AD and FTD patients compared to controls, in line with previous reports. Meta-analysis including 11 previously screened AD cohorts confirmed the association of p.R47H with AD (p = 2.93×10(-17)). Our data corroborate and extend previous findings to include an increased frequency of rare heterozygous TREM2 variations in AD and FTD, and show that TREM2 variants may play a role in neurodegenerative diseases in general.
ISSN: 0197-4580
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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