Journal
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
Volume 66, Issue 6, Pages 525-532Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.jnen.0000240476.73532.b0
Keywords
alpha-ketoglutarate dehydrogenase; cytochrome oxidase-1; immunoelectron microscopy; lipoic acid; proteolysis; pyruvate dehydrogenase; ultrastructure
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Funding
- NIA NIH HHS [AG024208] Funding Source: Medline
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Mitochondrial abnormalities are prominent in Alzheimer disease. In this study, 2 mitochondrial markers, cytochrome oxidase-1 and lipoic acid, a sulfur-containing cofactor required for the activity of several mitochondrial enzyme complexes, were compared using light and electron microscopic analyses and immunoblot assays. Both lipoic acid and cytochrome oxidase-1 immunoreactivity are increased in the cytoplasm of pyramidal neurons in Alzheimer disease compared with control cases. Of significance, lipoic acid was found to be strongly associated with granular structures, and ultrastructure analysis showed localization to mitochondria, cytosol, and, importantly, in organelles identified as autophagic vacuoles and lipofuscm in Alzheimer disease but not control cases. Cytochrome oxidase-1 immunoreactivity was limited to mitochondria and cytosol in both Alzheimer and control cases. These data suggest that mitochondria are key targets of increased autophagic degradation in Alzheimer disease. Whether increased autophagocytosis is a consequence of an increased turnover of mitochondria or whether the mitochondria in Alzheimer disease are more susceptible to autophagy remains to be resolved.
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