defects in mitochondrial dynamics and metabolomic signatures of evolving energetic stress in mouse models of familial alzheimers disease缺陷线粒体动力学和代谢组学特征的进化能量压力在家族性阿尔茨海默病小鼠模型.pdf

Defects in Mitochondrial Dynamics and Metabolomic Signatures of Evolving Energetic Stress in Mouse Models of Familial Alzheimer’s Disease 1 2 2 3 4 1 Eugenia Trushina *, Emirhan Nemutlu , Song Zhang , Trace Christensen , Jon Camp , Janny Mesa , 1 5 5 6 2 Ammar Siddiqui , Yasushi Tamura , Hiromi Sesaki , Thomas M. Wengenack , Petras P. Dzeja , Joseph F. Poduslo6 1 Department of Molecular Pharmacology and Experimental Therapeutics and Neurology, Mayo Clinic, Rochester, Minnesota, United States of America, 2 Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, United States of America, 3 Electron Microscopy Core Facility, Mayo Clinic, Rochester, Minnesota, United States of America, 4 Biomedical Imaging Resource, Mayo Clinic, Rochester, Minnesota, United States of America, 5 Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, 6 Departments of Neurology and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, United States of America Abstract Background: The identification of early mechanisms underlying Alzheimer’s Disease (AD) and associated biomarkers could advance development of new therapies and improve monitoring and predicting of AD progression. Mitochondrial dysfunction has been suggested to underlie AD pathophysiology, however, no comprehensive study exists that evaluates the effect of different familial AD (FAD) mutations on mitochondrial function, dynamics, and brain energetics. Methods and Findings: We characterized early mitochondrial dysfunction and metabolomic signatures of energetic stress in