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MAPT H1 haplotype is associated with late-onset Alzheimer's disease risk in APOE ε 4 noncarriers: Results from the dementia genetics Spanish consortium

AuthorsPastor, Pau; Bullido, María Jesús ; Sastre, Isabel ; Sánchez-Juan, Pascual
Alzheimer’s disease
frontotemporal dementia
genetic association
Issue Date2015
PublisherIOS Press
CitationJournal of Alzheimer's Disease 49: 343- 352 (2015)
AbstractThe MAPT H1 haplotype has been linked to several disorders, but its relationship with Alzheimer's disease (AD) remains controversial. A rare variant in MAPT (p.A152T) has been linked with frontotemporal dementia (FTD) and AD. We genotyped H1/H2 and p.A152T MAPT in 11,572 subjects from Spain (4,327 AD, 563 FTD, 648 Parkinson's disease (PD), 84 progressive supranuclear palsy (PSP), and 5,950 healthy controls). Additionally, we included 101 individuals from 21 families with genetic FTD. MAPT p.A152T was borderline significantly associated with FTD [odds ratio (OR)=2.03; p=0.063], but not with AD. MAPT H1 haplotype was associated with AD risk (OR=1.12; p=0.0005). Stratification analysis showed that this association was mainly driven by APOE ε4 noncarriers (OR=1.14; p=0.0025). MAPT H1 was also associated with risk for PD (OR=1.30; p=0.0003) and PSP (OR=3.18; p=8.59 × 10-8) but not FTD. Our results suggest that the MAPT H1 haplotype increases the risk of PD, PSP, and non-APOE ε4 AD.
Identifiersdoi: 10.3233/JAD-150555
issn: 1875-8908
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