title: Association between MAPT haplotype and memory function in patients with Parkinson's disease and healthy aging individuals.
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.
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; Department of Child and Adolescent Psychiatry, Institute of Psychiatry, King's College London, UK. Electronic address: sophie.winder-rhodes@doctors.org.uk.
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Winder-Rhodes
authors.affiliation: MRC Cognition and Brain Sciences Unit, Cambridge, UK; The Division of Brain Sciences, Department of Medicine, Imperial College, London, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Hampshire
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; MRC Cognition and Brain Sciences Unit, Cambridge, UK; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors.forename: James B
authors.initials: JB
authors.lastname: Rowe
authors.affiliation: Department of Otolaryngology, Washington University in St. Louis, St. Louis, MO, USA.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Peelle
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Robbins
authors.affiliation: MRC Cognition and Brain Sciences Unit, Cambridge, UK; The Brain and Mind Institute, The University of Western Ontario, London Ontario, Canada.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Owen
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK. Electronic address: rab46@cam.ac.uk.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Barker
mesh_terms: D000368:Aged; D000375:Aging / Q000235:genetics* / Q000523:psychology; D003071:Cognition / Q000502:physiology*; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology / Q000523:psychology*; D012306:Risk; D013702:Temporal Lobe / Q000473:pathology / Q000503:physiopathology; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins; D010100:Oxygen
keywords: Aging; Cognitive impairment; Dementia; Genetics; Hippocampus; MAPT; Memory; Parkinson's disease; Picture recognition; Tau; fMRI