Your browser doesn't support javascript.
loading
Genetic epistasis regulates amyloid deposition in resilient aging.
Felsky, Daniel; Xu, Jishu; Chibnik, Lori B; Schneider, Julie A; Knight, Jo; Kennedy, James L; Bennett, David A; De Jager, Philip L; Voineskos, Aristotle N.
Afiliação
  • Felsky D; Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Program in Translational NeuroPsychiatric Genomics, Department of
  • Xu J; Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
  • Chibnik LB; Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
  • Schneider JA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
  • Knight J; Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Data Science Institute and the Medical School, Lancaster Universi
  • Kennedy JL; Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
  • Bennett DA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
  • De Jager PL; Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
  • Voineskos AN; Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. Electronic address: aristotle.voineskos@camh.ca.
Alzheimers Dement ; 13(10): 1107-1116, 2017 Oct.
Article em En | MEDLINE | ID: mdl-28322202
ABSTRACT

INTRODUCTION:

The brain-derived neurotrophic factor (BDNF) interacts with important genetic Alzheimer's disease (AD) risk factors. Specifically, variants within the SORL1 gene determine BDNF's ability to reduce amyloid ß (Aß) in vitro. We sought to test whether functional BDNF variation interacts with SORL1 genotypes to influence expression and downstream AD-related processes in humans.

METHODS:

We analyzed postmortem brain RNA sequencing and neuropathological data for 441 subjects from the Religious Orders Study/Memory and Aging Project and molecular and structural neuroimaging data for 1285 subjects from the Alzheimer's Disease Neuroimaging Initiative.

RESULTS:

We found one SORL1 RNA transcript strongly regulated by SORL1-BDNF interactions in elderly without pathological AD and showing stronger associations with diffuse than neuritic Aß plaques. The same SORL1-BDNF interactions also significantly influenced Aß load as measured with [18F]Florbetapir positron emission tomography.

DISCUSSION:

Our results bridge the gap between risk and resilience factors for AD, demonstrating interdependent roles of established SORL1 and BDNF functional genotypes.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Peptídeos beta-Amiloides / Fator Neurotrófico Derivado do Encéfalo / Epistasia Genética / Doença de Alzheimer Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Limite: Aged / Aged80 / Female / Humans / Male Idioma: En Ano de publicação: 2017 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Peptídeos beta-Amiloides / Fator Neurotrófico Derivado do Encéfalo / Epistasia Genética / Doença de Alzheimer Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Limite: Aged / Aged80 / Female / Humans / Male Idioma: En Ano de publicação: 2017 Tipo de documento: Article