Dystrophic neurites of senile plaques in Alzheimer's disease are deficient in cytochrome c oxidase.
Double-labeling immunofluorescence and confocal microscopy have been used to learn about the local relationship between amyloid, mitochondria, and cytochrome c oxidase (COX) in dystrophic neurites of senile plaques in the frontal cortex in Alzheimer's disease (AD). Dystrophic neurites surrounding amyloid plaques are filled with mitochondrial porin-immunoreactive structures. In contrast with tangle-bearing and non-tangle-bearing neurons, which express mitochondrial porin and COX subunit 4, porin-immunoreactive neurites of senile plaques lack COX subunit 4. Parallel western blot studies in mitochondria-enriched fractions of the frontal cortex in the same cases disclosed reduced expression levels of COX, but not of prohibitin, in AD stages VB/C of Braak. Co-localization of porin and lysosomal associated protein 1, as revealed by double-labeling immunofluorescence and confocal microscopy, suggests that mitochondria may be engulfed by lysosomes in dystrophic neurites. These findings support a local link between amyloid deposition, abnormal mitochondria and impaired respiratory chain function (resulting from decrease of COX expression) in dystrophic neurites of senile plaques in AD.
Pérez-Gracia
Esther
E
Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Facultat de Medicina, Universitat de Barcelona, carrer Feixa LLarga sn, 08907 Hospitalet de LLobregat, Ciberned, Spain.
Torrejón-Escribano
Benjamín
B
Ferrer
Isidre
I
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D030401:Cytochrome-c Oxidase Deficiency / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005625:Frontal Lobe / Q000201:enzymology*; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000201:enzymology; D016501:Neurites / Q000201:enzymology*; D058225:Plaque, Amyloid / Q000201:enzymology*; D000091402:Prohibitins; D012097:Repressor Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000091402:Prohibitins; D012097:Repressor Proteins; D003576:Electron Transport Complex IV