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Dopamine receptor D4 (DRD4) polymorphisms with reduced functional potency intensify atrophy in syndrome-specific sites of frontotemporal dementia.
Butler, P M; Chiong, W; Perry, D C; Miller, Z A; Gennatas, E D; Brown, J A; Pasquini, L; Karydas, A; Dokuru, D; Coppola, G; Sturm, V E; Boxer, A L; Gorno-Tempini, M L; Rosen, H J; Kramer, J H; Miller, B L; Seeley, W W.
Afiliación
  • Butler PM; Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA. Electronic address: Monroe.Butler@ucsf.edu.
  • Chiong W; Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.
  • Perry DC; Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.
  • Miller ZA; Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.
  • Gennatas ED; Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.
  • Brown JA; Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.
  • Pasquini L; Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.
  • Karydas A; Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.
  • Dokuru D; Departments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
  • Coppola G; Departments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
  • Sturm VE; Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.
  • Boxer AL; Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.
  • Gorno-Tempini ML; Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.
  • Rosen HJ; Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.
  • Kramer JH; Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.
  • Miller BL; Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.
  • Seeley WW; Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.
Neuroimage Clin ; 23: 101822, 2019.
Article en En | MEDLINE | ID: mdl-31003069
OBJECTIVE: We aimed to understand the impact of dopamine receptor D4 (DRD4) polymorphisms on neurodegeneration in patients with dementia. We hypothesized that DRD4dampened-variants with reduced functional potency would be associated with greater atrophy in regions with higher receptor density. Given that DRD4 is concentrated in anterior regions of the limbic and cortical forebrain we anticipated genotype effects in patients with a more rostral pattern of neurodegeneration. METHODS: 337 subjects, including healthy controls, patients with Alzheimer's disease (AD) and frontotemporal dementia (FTD) underwent genotyping, structural MRI, and cognitive/behavioral testing. We conducted whole-brain voxel-based morphometry to examine the relationship between DRD4 genotypes and brain atrophy patterns within and across groups. General linear modeling was used to evaluate relationships between genotype and cognitive/behavioral measures. RESULTS: DRD4 dampened-variants predicted gray matter atrophy in disease-specific regions of FTD in anterior cingulate, ventromedial prefrontal, orbitofrontal and insular cortices on the right greater than the left. Genotype predicted greater apathy and repetitive motor disturbance in patients with FTD. These results covaried with frontoinsular cortical atrophy. Peak atrophy patterned along regions of neuroanatomic vulnerability in FTD-spectrum disorders. In AD subjects and controls, genotype did not impact gray matter intensity. CONCLUSIONS: We conclude that DRD4 polymorphisms with reduced functional potency exacerbate neuronal injury in sites of higher receptor density, which intersect with syndrome-specific regions undergoing neurodegeneration in FTD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Receptores de Dopamina D4 / Demencia Frontotemporal Tipo de estudio: Prognostic_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Neuroimage Clin Año: 2019 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Receptores de Dopamina D4 / Demencia Frontotemporal Tipo de estudio: Prognostic_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Neuroimage Clin Año: 2019 Tipo del documento: Article Pais de publicación: Países Bajos