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Association between MAPT haplotype and memory function in patients with Parkinson's disease and healthy aging individuals.


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Authors

Winder-Rhodes, Sophie E 
Hampshire, Adam 
Rowe, James B 
Peelle, Jonathan E 
Robbins, Trevor W 

Abstract

Genetic variation is associated with differences in the function of the brain as well as its susceptibility to disease. The common H1 haplotypic variant of the microtubule-associated protein tau gene (MAPT) has been related to an increased risk for Parkinson's disease (PD). Furthermore, among PD patients, H1 homozygotes have an accelerated progression to dementia. We investigated the neurocognitive correlates of MAPT haplotypes using functional magnetic resonance imaging. Thirty-seven nondemented patients with PD (19 H1/H1, 18 H2 carriers) and 40 age-matched controls (21 H1/H1, 19 H2 carriers) were scanned during performance of a picture memory encoding task. Behaviorally, H1 homozygosity was associated with impaired picture recognition memory in PD patients and control subjects. These impairments in the H1 homozygotes were accompanied by an altered blood-oxygen level-dependent response in the medial temporal lobe during successful memory encoding. Additional age-related differences in blood-oxygen level-dependent response were observed in the medial temporal lobes of H1 homozygotes with PD. These results suggest that common variation in MAPT is not only associated with the dementia of PD but also differences in the neural circuitry underlying aspects of cognition in normal aging.

Description

Keywords

Aging, Cognitive impairment, Dementia, Genetics, Hippocampus, MAPT, Memory, Parkinson's disease, Picture recognition, Tau, fMRI, Aged, Aging, Cognition, Disease Progression, Female, Genetic Association Studies, Genetic Predisposition to Disease, Haplotypes, Humans, Magnetic Resonance Imaging, Male, Memory, Middle Aged, Oxygen, Parkinson Disease, Risk, Temporal Lobe, tau Proteins

Journal Title

Neurobiol Aging

Conference Name

Journal ISSN

0197-4580
1558-1497

Volume Title

36

Publisher

Elsevier Inc.
Sponsorship
Medical Research Council (G0001354)
Wellcome Trust (088324/Z/09/Z)
Medical Research Council (MC_U105597119)
Wellcome Trust (103838/Z/14/Z)
This work was funded by Parkinson's UK, the Medical Research Council, the Wellcome Trust (088324), and the NIHR Comprehensive Biomedical Research Centre (RG64473). The BCNI is co-funded by the MRC and Wellcome Trust. Sophie E. Winder-Rhodes received PhD funding from a Merck Sharp and Dohme studentship.