RT Journal Article
SR Electronic
T1 An evaluation of the impact of <em>MAPT</em>, <em>SNCA</em> and <em>APOE</em> on the burden of Alzheimer's and Lewy body pathology
JF Journal of Neurology, Neurosurgery &amp; Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 424
OP 429
DO 10.1136/jnnp-2011-301413
VO 83
IS 4
A1 Wider, Christian
A1 Ross, Owen A
A1 Nishioka, Kenya
A1 Heckman, Michael G
A1 Vilariño-Güell, Carles
A1 Jasinska-Myga, Barbara
A1 Erketin-Taner, Nilufer
A1 Rademakers, Rosa
A1 Graff-Radford, Neill R
A1 Mash, Deborah C
A1 Papapetropoulos, Spiridon
A1 Duara, Ranjan
A1 Uchikado, Hirotake
A1 Wszolek, Zbigniew K
A1 Farrer, Matthew J
A1 Dickson, Dennis W
YR 2012
UL http://jnnp.bmj.com/content/83/4/424.abstract
AB 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&lt;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.