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Common and rare TBK1 variants in early-onset Alzheimer disease in a European cohort
J. Verheijen, J. van der Zee, I. Gijselinck, T. Van den Bossche, L. Dillen, B. Heeman, E. Gómez-Tortosa, A. Lladó, R. Sanchez-Valle, C. Graff, P. Pastor, MA. Pastor, L. Benussi, R. Ghidoni, G. Binetti, J. Clarimon, A. de Mendonça, E. Gelpi, M....
Neurobiology of aging.
2018 ;
62 (-) :
245.e1-245.e7.
[pub] 20171025
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
Perzistentní odkaz
https://www.medvik.cz/link/bmc18033552
- MeSH
- alely MeSH
- Alzheimerova nemoc genetika MeSH
- amyotrofická laterální skleróza genetika MeSH
- frontotemporální demence genetika MeSH
- genetická variace genetika MeSH
- genetické asociační studie * MeSH
- heterozygot MeSH
- homozygot MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace ztráty funkce genetika MeSH
- protein-serin-threoninkinasy genetika MeSH
- riziko MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
TANK-binding kinase 1 (TBK1) loss-of-function (LoF) mutations are known to cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), often combined with memory deficits early in the disease course. We performed targeted resequencing of TBK1 in 1253 early onset Alzheimer's disease (EOAD) patients from 8 European countries to investigate whether pathogenic TBK1 mutations are enriched among patients with clinical diagnosis of EOAD. Variant frequencies were compared against 2117 origin-matched controls. We identified only 1 LoF mutation (p.Thr79del) in a patient clinically diagnosed with Alzheimer's disease and a positive family history of ALS. We did not observe enrichment of rare variants in EOAD patients compared to controls, nor of rare variants affecting NFκB induction. Of 3 common coding variants, rs7486100 showed evidence of association (OR 1.46 [95% CI 1.13-1.9]; p-value 0.01). Homozygous carriers of the risk allele showed reduced expression of TBK1 (p-value 0.03). Our findings are not indicative of a significant role for TBK1 mutations in EOAD. The association between common variants in TBK1, disease risk and reduced TBK1 expression warrants follow-up in FTD/ALS cohorts.
3rd Department of Neurology Medical School Aristotle University of Thessaloniki Thessaloniki Greece
Center for Neuroscience and Cell Biology University of Coimbra Coimbra Portugal
Department of Geriatric Medicine Genetics Unit Karolinska University Hospital Stockholm Sweden
Department of Neurology Antwerp University Hospital Edegem Belgium
Department of Neurology Fundación Jiménez Díaz Madrid Spain
Department of Neurology University Hospitals Leuven Leuven Belgium
Department of Neurosciences Faculty of Medicine KU Leuven Leuven Belgium
Department of Psychiatry and Psychotherapy Technische Universität München München Germany
Faculty of Medicine University of Lisbon Lisbon Portugal
Fundació ACE Institut Català de Neurociències Aplicades Barcelona Spain
Citace poskytuje Crossref.org
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