An evaluation of the impact of MAPT, SNCA and APOE on the burden of Alzheimer's and Lewy body pathology.

Details

Serval ID
serval:BIB_59394BAFC092
Type
Article: article from journal or magazin.
Collection
Publications
Title
An evaluation of the impact of MAPT, SNCA and APOE on the burden of Alzheimer's and Lewy body pathology.
Journal
Journal of Neurology, Neurosurgery, and Psychiatry
Author(s)
Wider C., Ross O.A., Nishioka K., Heckman M.G., Vilariño-Güell C., Jasinska-Myga B., Erketin-Taner N., Rademakers R., Graff-Radford N.R., Mash D.C., Papapetropoulos S., Duara R., Uchikado H., Wszolek Z.K., Farrer M.J., Dickson D.W.
ISSN
1468-330X (Electronic)
ISSN-L
0022-3050
Publication state
Published
Issued date
2012
Volume
83
Number
4
Pages
424-429
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
PURPOSE: 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.
CONCLUSION: 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.
Keywords
Aged, 80 and over, Alzheimer Disease/genetics, Alzheimer Disease/pathology, Apolipoproteins E/genetics, Brain/pathology, Female, Haplotypes, Humans, Lewy Bodies/pathology, Lewy Body Disease/genetics, Lewy Body Disease/pathology, Male, Organ Size, Parkinson Disease/genetics, Parkinson Disease/pathology, Polymorphism, Single Nucleotide, alpha-Synuclein/genetics, tau Proteins/genetics
Pubmed
Web of science
Create date
12/02/2013 15:51
Last modification date
20/08/2019 15:12
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