title: Coenzyme Q10 decreases amyloid pathology and improves behavior in a transgenic mouse model of Alzheimer's disease.
abstract: Increased oxidative stress is implicated in the pathogenesis of Alzheimer's disease (AD). A large body of evidence suggests that mitochondrial dysfunction and increased reactive oxygen species occur prior to amyloid-β (Aβ) deposition. Coenzyme Q10 (CoQ10), a component of the mitochondrial electron transport chain, is well characterized as a neuroprotective antioxidant in animal models and human trials of Huntington's disease and Parkinson's disease, and reduces plaque burden in AβPP/PS1 mice. We now show that CoQ10 reduces oxidative stress and amyloid pathology and improves behavioral performance in the Tg19959 mouse model of AD. CoQ10 treatment decreased brain levels of protein carbonyls, a marker of oxidative stress. CoQ10 treatment resulted in decreased plaque area and number in hippocampus and in overlying cortex immunostained with an Aβ42-specific antibody. Brain Aβ42 levels were also decreased by CoQ10 supplementation. Levels of amyloid-β protein precursor (AβPP) β-carboxyterminal fragments were decreased. Importantly, CoQ10-treated mice showed improved cognitive performance during Morris water maze testing. Our results show decreased pathology and improved behavior in transgenic AD mice treated with the naturally occurring antioxidant compound CoQ10. CoQ10 is well tolerated in humans and may be promising for therapeutic trials in AD.
authors.affiliation: Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Magali
authors.initials: M
authors.lastname: Dumont
authors.forename: Khatuna
authors.initials: K
authors.lastname: Kipiani
authors.forename: Fangmin
authors.initials: F
authors.lastname: Yu
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Wille
authors.forename: Maya
authors.initials: M
authors.lastname: Katz
authors.forename: Noel Y
authors.initials: NY
authors.lastname: Calingasan
authors.forename: Gunnar K
authors.initials: GK
authors.lastname: Gouras
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lin
authors.forename: M Flint
authors.initials: MF
authors.lastname: Beal
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000178:diet therapy* / Q000235:genetics; D000682:Amyloid / Q000187:drug effects; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001526:Behavioral Symptoms / Q000188:drug therapy* / Q000209:etiology; D003072:Cognition Disorders / Q000178:diet therapy / Q000209:etiology; D004797:Enzyme-Linked Immunosorbent Assay; D005106:Exploratory Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology; D009154:Mutation / Q000235:genetics; D009447:Neuroblastoma / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D050050:Protein Carbonylation / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014815:Vitamins / Q000627:therapeutic use*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D014815:Vitamins; C075222:amyloid beta-protein (1-42); D014451:Ubiquinone; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse; C024989:coenzyme Q10