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Alzheimers Dement. 2015 Oct;11(10):1153-62. doi: 10.1016/j.jalz.2014.10.011. Epub 2014 Dec 10.

Carriers of a common variant in the dopamine transporter gene have greater dementia risk, cognitive decline, and faster ventricular expansion.

Author information

1
Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Imaging Genetics Center, Institute for Neuroimaging and Informatics, Department of Neurology, Keck/USC School of Medicine, University of Southern California, Los Angeles, CA, USA.
2
Imaging Genetics Center, Institute for Neuroimaging and Informatics, Department of Neurology, Keck/USC School of Medicine, University of Southern California, Los Angeles, CA, USA.
3
Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
4
Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Imaging Genetics Center, Institute for Neuroimaging and Informatics, Department of Neurology, Keck/USC School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Departments of Psychiatry, Engineering, Radiology, & Ophthalmology, Keck/USC School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: pthomp@usc.edu.

Abstract

INTRODUCTION:

Genetic variants in DAT1, the gene encoding the dopamine transporter (DAT) protein, have been implicated in many brain disorders. In a recent case-control study of Alzheimer's disease (AD), a regulatory polymorphism in DAT1 showed a significant association with the clinical stages of dementia.

METHODS:

We tested whether this variant was associated with increased AD risk, and with measures of cognitive decline and longitudinal ventricular expansion, in a large sample of elderly participants with genetic, neurocognitive, and neuroimaging data from the Alzheimer's Disease Neuroimaging Initiative.

RESULTS:

The minor allele-previously linked with increased DAT expression in vitro-was more common in AD patients than in both individuals with mild cognitive impairment and healthy elderly controls. The same allele was also associated with poorer cognitive performance and faster ventricular expansion, independently of diagnosis.

DISCUSSION:

These results may be due to reduced dopaminergic transmission in carriers of the DAT1 mutation.

KEYWORDS:

DAT1; Dementia; Dopamine transporter; Neuroimaging genetics; Ventricular expansion

PMID:
25496873
PMCID:
PMC4465053
DOI:
10.1016/j.jalz.2014.10.011
[Indexed for MEDLINE]
Free PMC Article

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