Your browser doesn't support javascript.
loading
Late-onset Alzheimer's disease is associated with inherent changes in bioenergetics profiles.
Sonntag, Kai-C; Ryu, Woo-In; Amirault, Kristopher M; Healy, Ryan A; Siegel, Arthur J; McPhie, Donna L; Forester, Brent; Cohen, Bruce M.
Afiliação
  • Sonntag KC; Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA. ksonntag@mclean.harvard.edu.
  • Ryu WI; Basic Neuroscience Division, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA. ksonntag@mclean.harvard.edu.
  • Amirault KM; Program for Neuropsychiatric Research, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA. ksonntag@mclean.harvard.edu.
  • Healy RA; Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
  • Siegel AJ; Basic Neuroscience Division, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
  • McPhie DL; Program for Neuropsychiatric Research, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
  • Forester B; Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
  • Cohen BM; Basic Neuroscience Division, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
Sci Rep ; 7(1): 14038, 2017 10 25.
Article em En | MEDLINE | ID: mdl-29070876
Body-wide changes in bioenergetics, i.e., energy metabolism, occur in normal aging and disturbed bioenergetics may be an important contributing mechanism underlying late-onset Alzheimer's disease (LOAD). We investigated the bioenergetic profiles of fibroblasts from LOAD patients and healthy controls, as a function of age and disease. LOAD cells exhibited an impaired mitochondrial metabolic potential and an abnormal redox potential, associated with reduced nicotinamide adenine dinucleotide metabolism and altered citric acid cycle activity, but not with disease-specific changes in mitochondrial mass, production of reactive oxygen species, transmembrane instability, or DNA deletions. LOAD fibroblasts demonstrated a shift in energy production to glycolysis, despite an inability to increase glucose uptake in response to IGF-1. The increase of glycolysis and the abnormal mitochondrial metabolic potential in LOAD appeared to be inherent, as they were disease- and not age-specific. Our findings support the hypothesis that impairment in multiple interacting components of bioenergetic metabolism may be a key mechanism contributing to the risk and pathophysiology of LOAD.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Metabolismo Energético / Doença de Alzheimer Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Metabolismo Energético / Doença de Alzheimer Idioma: En Ano de publicação: 2017 Tipo de documento: Article