title: Carriers of a common variant in the dopamine transporter gene have greater dementia risk, cognitive decline, and faster ventricular expansion.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  These results may be due to reduced dopaminergic transmission in carriers of the DAT1 mutation.
authors.affiliation: 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.
authors.forename: Florence F
authors.initials: FF
authors.lastname: Roussotte
authors.affiliation: Imaging Genetics Center, Institute for Neuroimaging and Informatics, Department of Neurology, Keck/USC School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Boris A
authors.initials: BA
authors.lastname: Gutman
authors.affiliation: Imaging Genetics Center, Institute for Neuroimaging and Informatics, Department of Neurology, Keck/USC School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Derrek P
authors.initials: DP
authors.lastname: Hibar
authors.affiliation: Imaging Genetics Center, Institute for Neuroimaging and Informatics, Department of Neurology, Keck/USC School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Madsen
authors.affiliation: 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.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Narr
authors.affiliation: 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.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics; D016022:Case-Control Studies; D002552:Cerebral Ventricles / Q000473:pathology*; D003071:Cognition; D060825:Cognitive Dysfunction / Q000235:genetics; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human
keywords: DAT1; Dementia; Dopamine transporter; Neuroimaging genetics; Ventricular expansion