An evaluation of the impact of MAPT, SNCA and APOE on the burden of Alzheimer's and Lewy body pathology (original) (raw)

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

Christian Wider1,2,
Owen A Ross1,
Kenya Nishioka1,
Michael G Heckman3,
Carles Vilariño-Güell1,
Barbara Jasinska-Myga1,4,
Nilufer Erketin-Taner1,
Rosa Rademakers1,
Neill R Graff-Radford2,
Deborah C Mash5,
Spiridon Papapetropoulos5,
Ranjan Duara6,
Hirotake Uchikado7,
Zbigniew K Wszolek2,
Matthew J Farrer1,
Dennis W Dickson7
1Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA
2Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA
3Biostatistics Unit, Mayo Clinic, Jacksonville, Florida, USA
4Department of Neurology, Medical University of Silesia, Katowice, Poland
5Department of Neurology, School of Medicine, University of Miami, Miami, Florida, USA
6Wien Center for Alzheimer's Disease and Memory Disorders, Mt Sinai Medical Center, Miami Beach, Florida, USA
7Departments of Pathology and Neuroscience, Mayo Clinic, Jacksonville, Florida, USA
Correspondence to Dr D W Dickson, Neuropathology Laboratory, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA; dickson.dennis{at}mayo.edu

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.

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.