Autophagocytosis of mitochondria is prominent in Alzheimer disease.
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 lipofuscin 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.
Moreira
Paula I
PI
Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
Siedlak
Sandra L
SL
Wang
Xinglong
X
Santos
Maria S
MS
Oliveira
Catarina R
CR
Tabaton
Massimo
M
Nunomura
Akihiko
A
Szweda
Luke I
LI
Aliev
Gjumrakch
G
Smith
Mark A
MA
Zhu
Xiongwei
X
Perry
George
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001343:Autophagy; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002648:Child; D003593:Cytoplasm / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000378:metabolism; D008062:Lipofuscin / Q000378:metabolism; D008854:Microscopy, Electron; D008875:Middle Aged; D008928:Mitochondria; D015388:Organelles / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism; D008063:Thioctic Acid / Q000378:metabolism; D014018:Tissue Distribution
D007527:Isoenzymes; D008062:Lipofuscin; D008063:Thioctic Acid; D003576:Electron Transport Complex IV