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

Sophie E Winder-Rhodes,Adam Hampshire,James B Rowe,Jonathan E Peelle,Trevor W Robbins,Adrian M Owen,Roger A Barker

doi:10.1016/j.neurobiolaging.2014.12.006

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.

Highlights

Neurodegenerative diseases of the central nervous system represent a formidable challenge in our aging society
The aim of this study was to define differences associated with common haplotypic variation in microtubule-associated protein tau gene (MAPT) during memory formation in patients with Parkinson’s disease (PD) and healthy age-matched control subjects
This is the first study to investigate the neurocognitive correlates of haplotypic variation in MAPT in patients with PD and control subjects using functional magnetic resonance imaging (fMRI), and we anticipate that our findings will contribute to our understanding of the relationship between this common genetic variant, cognitive dysfunction, and dementia in PD

Summary

Introduction

Neurodegenerative diseases of the central nervous system represent a formidable challenge in our aging society. Parkinson’s disease (PD) affects 1%e2% of the population over the age of 65 years, and it is classically regarded as a movement disorder, associated cognitive impairment is a key determinant of quality of life and care requirements. The executive cognitive deficits in PD are thought to be related to disturbances in frontostriatal dopaminergic systems (Williams-Gray et al, 2007), but there is substantial evidence linking aspects of PD dementia to the progression of a “posterior cortical” syndrome of cognitive impairment (Williams-Gray et al, 2009) and the spread of Lewy body-type pathology into cortical and limbic structures (Aarsland et al, 2005). Genetic association studies have identified the gene encoding the microtubule-associated protein tau, MAPT, as a key risk locus for several neurodegenerative disorders including PD (Caffrey and Wade-Martins, 2007).

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