Affiliations: [a] Harvey Cushing Institutes of Neuroscience, North Shore-Long Island Jewish Health System, Great Neck, NY 11021, USA | [b] Department of Pathology and Surgery, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA | Department of Pathology, Case Western Reserve University, Cleveland, OH, USA
Correspondence:
[*]
Corresponding author: Dr. Shi Du Yan, Department of Pathology, Surgery, and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physician & Surgeons, Columbia University, 650 West 168th Street, BB17-07, New York, NY 10032, USA. Tel.: +1 212 342 1304; Fax: +1 212 305 5337; E-mail: sdy1@columbia.edu.
Abstract: As an important molecule in the pathogenesis of Alzheimer's disease (AD), amyloid-β (Aβ) interferes with multiple aspects of mitochondrial function, including energy metabolism failure, production of reactive oxygen species (ROS) and permeability transition pore formation. Recent studies have demonstrated that Aβ progressively accumulates within mitochondrial matrix, providing a direct link to mitochondrial toxicity. Aβ-binding alcohol dehydrogenase (ABAD) is localized to the mitochondrial matrix and binds to mitochondrial Aβ. Interaction of ABAD with Aβ exaggerates Aβ-mediated mitochondrial and neuronal perturbation, leading to impaired synaptic function, and dysfunctional spatial learning/memory. Thus, blockade of ABAD/Aβ interaction may be a potential therapeutic strategy for AD.
Keywords: Alzheimer's disease, amyloid-β, mitochondria, energy metabolism, ABAD
