TY - JOUR 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 SP - 424 LP - 429 DO - 10.1136/jnnp-2011-301413 VL - 83 IS - 4 AU - Christian Wider AU - Owen A Ross AU - Kenya Nishioka AU - Michael G Heckman AU - Carles Vilariño-Güell AU - Barbara Jasinska-Myga AU - Nilufer Erketin-Taner AU - Rosa Rademakers AU - Neill R Graff-Radford AU - Deborah C Mash AU - Spiridon Papapetropoulos AU - Ranjan Duara AU - Hirotake Uchikado AU - Zbigniew K Wszolek AU - Matthew J Farrer AU - Dennis W Dickson Y1 - 2012/04/01 UR - http://jnnp.bmj.com/content/83/4/424.abstract N2 - 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. ER -