title: An evaluation of the impact of MAPT, SNCA and APOE on the burden of Alzheimer's and Lewy body pathology.
abstract: OBJECTIVE
  The study investigates the effects of genetic factors on the pathology of Alzheimer's disease (AD) and Lewy body (LB) diseases, including Parkinson's disease and dementia with Lewy bodies.
  
  
  METHODS
  A multicentre autopsy series (762 brain samples) with AD, LB or vascular pathology was examined. The effects of the tau gene (MAPT) H1 haplotype, the H1 specific SNP rs242557, APOE and the α-synuclein gene (SNCA) 3'UTR SNP rs356165 on the burden of AD and LB pathology were assessed. Neurofibrillary tangles (NFTs) were counted in four brain regions, senile plaques in five and LBs in four. Braak NFT stage, brain weight and presence of vascular pathology were also documented.
  
  
  RESULTS
  MAPT H1 associated with lower counts of NFTs in the middle frontal (p<0.001) and inferior parietal (p=0.005) cortices, and also with lower counts of senile plaques in the motor cortex (p=0.001). Associations of MAPT H1 with increased LB counts in the middle frontal cortex (p=0.011) and inferior parietal cortex (p=0.033) were observed but were not significant after multiple testing adjustment. The APOE ε4 allele was strongly associated with overall Alzheimer type pathology (all p≤0.001). SNCA rs356165 and the MAPT H1 specific SNP rs242557 did not associate with AD or LB pathology.
  
  
  CONCLUSIONS
  This study shows for the first time that MAPT H1 is associated with reduced Alzheimer type pathology which could have important implications for the understanding of disease mechanisms and their genetic determinants.
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Wider
authors.forename: Owen A
authors.initials: OA
authors.lastname: Ross
authors.forename: Kenya
authors.initials: K
authors.lastname: Nishioka
authors.forename: Michael G
authors.initials: MG
authors.lastname: Heckman
authors.forename: Carles
authors.initials: C
authors.lastname: Vilariño-Güell
authors.forename: Barbara
authors.initials: B
authors.lastname: Jasinska-Myga
authors.forename: Nilufer
authors.initials: N
authors.lastname: Erketin-Taner
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.forename: Neill R
authors.initials: NR
authors.lastname: Graff-Radford
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Mash
authors.forename: Spiridon
authors.initials: S
authors.lastname: Papapetropoulos
authors.forename: Ranjan
authors.initials: R
authors.lastname: Duara
authors.forename: Hirotake
authors.initials: H
authors.lastname: Uchikado
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farrer
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000473:pathology; D005260:Female; D006239:Haplotypes; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology; D020961:Lewy Body Disease / Q000235:genetics* / Q000473:pathology*; D008297:Male; D009929:Organ Size; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D051844:alpha-Synuclein / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; C054369:MAPT protein, human; C497604:SNCA protein, human; D051844:alpha-Synuclein; D016875:tau Proteins