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

NEUROBIOLOGY OF AGING

卷:36

Article

Winder-Rhodes, Sophie E.^1,2  Hampshire, Adam^3,4  Rowe, James B.^1,3,5  Peelle, Jonathan E.⁶  Robbins, Trevor W.⁵  Owen, Adrian M.^3,7  Barker, Roger A.^1,5 

[1] Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 0PY, England

[2] Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, London WC2R 2LS, England

[3] MRC, Cognit & Brain Sci Unit, Cambridge, England

[4] Univ London Imperial Coll Sci Technol & Med, Dept Med, Div Brain Sci, London, England

[5] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge, England

[6] Washington Univ, Dept Otolaryngol, St Louis, MO USA

[7] Univ Western Ontario, Brain & Mind Inst, London, ON, Canada

关键词: Parkinson's disease;    Dementia;    Aging;    Memory;    fMRI;    Hippocampus;    MAPT;    Genetics;    Tau;    Cognitive impairment;    Picture recognition;   

DOI  :  10.1016/j.neurobiolaging.2014.12.006

来源: Elsevier

【 摘 要 】

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. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license.

【 授权许可】

Free