Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

We investigated the genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD). Using summary statistics (P-values) from large recent genome-wide association studies (GWAS) (total n=89 904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with both AD and PD. We found and replicated association of both AD and PD with the A allele of rs393152 within the extended MAPT region on chromosome 17 (meta analysis P-value across five independent AD cohorts=1.65 × 10(-7)). In independent datasets, we found a dose-dependent effect of the A allele of rs393152 on intra-cerebral MAPT transcript levels and volume loss within the entorhinal cortex and hippocampus. Our findings identify the tau-associated MAPT locus as a site of genetic overlap between AD and PD, and extending prior work, we show that the MAPT region increases risk of Alzheimer's neurodegeneration.

Original publication

DOI

10.1038/mp.2015.6

Type

Journal article

Journal

Molecular psychiatry

Publication Date

12/2015

Volume

20

Pages

1588 - 1595

Addresses

Department of Radiology, University of California, San Diego, La Jolla, CA, USA.

Keywords

ADNI, ADGC, GERAD, CHARGE and IPDGC Investigators, Brain, Chromosomes, Human, Pair 17, Humans, Parkinson Disease, Alzheimer Disease, Apolipoproteins E, tau Proteins, Polymorphism, Single Nucleotide, Alleles, Aged, Aged, 80 and over, Middle Aged, Female, Male, Genome-Wide Association Study, Genetic Loci, Genetic Pleiotropy