title: Mitochondrial bioenergetics is defective in presymptomatic Tg2576 AD mice.
abstract: Alzheimer's disease (AD) is an age-related dementia, with the pathological hallmarks of neuritic plaques and neurofibrillary tangles, brain atrophy and loss of synaptic terminals. Dysfunctional mitochondrial bioenergetics is implicated as a contributing factor to the cognitive decline observed in AD. We hypothesized that, in the presence of the AD neurotoxic peptide beta-amyloid, mitochondrial respiration is impaired early in synaptic terminals, which are vital to cognitive performance, preferentially in cognitive centers of the brain. We compared oxygen consumption in synaptosomal and perikaryal mitochondria prepared from the cerebral cortex and cerebellum of wild type (WT) and AD transgenic Tg2576 mice. Compared to WT mice, Tg2576 mice showed decreased mitochondrial respiration in the cerebral cortex specifically in synaptosomal fraction, while the perikaryal mitochondria were unaffected. Neither mitochondrial fraction was affected in the cerebellum of Tg2576 mice as compared to WT. The occurrence of a bioenergetic defect in synaptic terminals of mice overexpressing mutant beta-amyloid, in particular in an area of the brain important to cognition, points to an early role of mitochondrial defects in the onset of cognitive deficits in AD.
authors.affiliation: Department of Neurology, The Mount Sinai School of Medicine, New York, NY 10029, USA ; Geriatrics Research, Education and Clinical Center, James J. Peters Veterans Affairs, Medical Center, Bronx, NY 10468, USA.
authors.forename: Merina
authors.initials: M
authors.lastname: Varghese
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Alice
authors.initials: A
authors.lastname: Cheng
authors.forename: Xianjuan
authors.initials: X
authors.lastname: Qian
authors.forename: Amna
authors.initials: A
authors.lastname: Chaudhry
authors.forename: Lap
authors.initials: L
authors.lastname: Ho
authors.forename: Giulio Maria
authors.initials: GM
authors.lastname: Pasinetti
keywords: Alzheimer’s disease; Amyloid; Dementia; Energy Metabolism; Memory; Mitochondria; Oxidative phosphorylation; Oxygen Consumption; Tg2576