title: The dying of the light: mitochondrial failure in Alzheimer's disease.
abstract: Impaired brain energy production, reflected by reduced cortical glucose metabolism seen on 2-FDG PET scans, has emerged as a robust biomarker of mild cognitive impairment (MCI). Progression from MCI to Alzheimer's disease (AD) shows further decline of cortical 2-FDG uptake, implying worsening bioenergetics. We characterized respiration, respiratory protein levels, and gene expressions for mitochondrial DNA (mtDNA), mitochondrial biogenesis, and antioxidative signaling in preparations from postmortem AD and control frontal cortex. Mitochondrial respiration was maintained in frozen brain mitochondria and reduced by approximately two-thirds in AD due to loss of mitochondrial mass. Levels of most respiratory proteins were preserved, but expressions of gene families for mtDNA, mitobiogenesis, and mitochondrial/cytosolic antioxidant enzymes were reduced in AD cortex. None of these changes in AD were related to elevated levels of amyoid-β1-42 peptide. For unclear reasons, mitochondrial biogenesis is suppressed in AD frontal cortex, leading to reduced mitochondrial mass and impaired mitochondrial respiratory capacity. Downregulation of antioxidant proteins further threatens neuronal function. Altering progression of AD appears to require both correction of impaired mitobiogenesis and restoration of antioxidant protection.
authors: Neuroscience Graduate Program and Medical Scientist Training Program, University of Virginia School of Medicine, Charlottesville, VA, USA.
authors: Kisha J
authors: KJ
authors: Young-Collier
authors: Michael
authors: M
authors: McArdle
authors: James P
authors: JP
authors: Bennett
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D019069:Cell Respiration / Q000502:physiology; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D028361:Mitochondrial Diseases / Q000378:metabolism* / Q000473:pathology
chemical_list: D004272:DNA, Mitochondrial