An evaluation of the impact ofMAPT,SNCAandAPOEon the burden of Alzheimer's and Lewy body pathology
- 30 January 2012
- journal article
- cognitive disorders
- Published by BMJ in Journal of Neurology, Neurosurgery & Psychiatry
- Vol. 83 (4), 424-429
- https://doi.org/10.1136/jnnp-2011-301413
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 (pMAPT 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.This publication has 38 references indexed in Scilit:
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