MAPT H1 Haplotype is Associated with Late-Onset Alzheimer's Disease Risk in APOEɛ4 Noncarriers: Results from the Dementia Genetics Spanish Consortium

J Alzheimers Dis. 2016;49(2):343-52. doi: 10.3233/JAD-150555.

Abstract

The 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 ɛ4 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 ɛ4 AD.

Keywords: A152T; Alzheimer’s disease; H1H2; MAPT; frontotemporal dementia; genetic association.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics*
  • Apolipoprotein E4 / genetics
  • Female
  • Frontotemporal Dementia / genetics
  • Genetic Predisposition to Disease / genetics*
  • Haplotypes
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Spain
  • tau Proteins / genetics*

Substances

  • Apolipoprotein E4
  • MAPT protein, human
  • tau Proteins