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 surroundi...

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Bibliographic Details
Published in:Acta neuropathologica 2008-09, Vol.116 (3), p.261-268
Main Authors: Pérez-Gracia, Esther, Torrejón-Escribano, Benjamín, Ferrer, Isidre
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Alzheimer Disease - enzymology
Alzheimer's disease
Amyloid beta-Peptides - metabolism
Brain
Cytochrome
Cytochrome-c Oxidase Deficiency - metabolism
Dehydrogenases
Dementia
Electron Transport Complex IV - metabolism
Female
Fluorescent Antibody Technique, Indirect
Frontal Lobe - enzymology
Humans
Labeling
Male
Medicine
Medicine & Public Health
Metabolism
Microscopy
Microscopy, Confocal
Mitochondria
Mitochondria - enzymology
Mitochondrial DNA
Neurites - enzymology
Neuropathology
Neurosciences
Original Paper
Pathology
Plaque, Amyloid - enzymology
Proteins
Repressor Proteins - metabolism
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Summary: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.
ISSN:0001-6322
1432-0533
DOI:10.1007/s00401-008-0370-6