COMT Val158Met genotype influences neurodegeneration within dopamine-innervated brain structures.

Neurology
E D GennatasW W Seeley

Abstract

We sought to determine whether the Val(158)Met polymorphism in the catechol-O-methyltransferase (COMT) gene influences neurodegeneration within dopamine-innervated brain regions. A total of 252 subjects, including healthy controls and patients with Alzheimer disease, behavioral variant frontotemporal dementia, and semantic dementia, underwent COMT genotyping and structural MRI. Whole-brain voxel-wise regression analyses revealed that COMT Val(158)Met Val allele dosage, known to produce a dose-dependent decrease in synaptic dopamine (DA) availability, correlated with decreased gray matter in the region of the ventral tegmental area (VTA), ventromedial prefrontal cortex, bilateral dorsal midinsula, left dorsolateral prefrontal cortex, and right ventral striatum. Unexpectedly, patients carrying a Met allele showed greater VTA volumes than age-matched controls. Gray matter intensities within COMT-related brain regions correlated with cognitive and behavioral deficits. The results are consistent with the hypothesis that increased synaptic DA catabolism promotes neurodegeneration within DA-innervated brain regions.

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Citations

Aug 1, 2012·Current Neurology and Neuroscience Reports·Masood Manoochehri, Edward D Huey
Mar 2, 2013·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Antonio Verdejo-GarcíaRafael de la Torre
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Jan 27, 2016·Journal of the Neurological Sciences·Weiqian YanBeisha Tang
Dec 11, 2014·International Journal of Geriatric Psychiatry·Nobuto ShibataHeii Arai
Apr 17, 2015·BMC Neurology·Jennifer S YokoyamaGiovanni Coppola
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Nov 2, 2016·Frontiers in Behavioral Neuroscience·Laura Del HoyoUNKNOWN TESDAD Study Group
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May 14, 2020·The Journal of Neuropsychiatry and Clinical Neurosciences·Edward D HueyJordan Grafman
Mar 30, 2020·The Journal of Nervous and Mental Disease·Edward D Huey

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