Dystrophic neurites of senile plaques in Alzheimer's disease are deficient in cytochrome c oxidase.

Abstract

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.

• Authors: Esther Pérez-Gracia, Benjamín Torrejón-Escribano, Isidre Ferrer
• Journal: Acta neuropathologica (Acta Neuropathol) Vol. 116 Issue 3 Pg. 261-8 (Sep 2008) ISSN: 1432-0533 [Electronic] Germany
• PMID: 18629521 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Prohibitins
• Repressor Proteins
• Electron Transport Complex IV

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (enzymology)
• Amyloid beta-Peptides (metabolism)
• Cytochrome-c Oxidase Deficiency (metabolism)
• Electron Transport Complex IV (metabolism)
• Female
• Fluorescent Antibody Technique, Indirect
• Frontal Lobe (enzymology)
• Humans
• Male
• Microscopy, Confocal
• Mitochondria (enzymology)
• Neurites (enzymology)
• Plaque, Amyloid (enzymology)
• Prohibitins
• Repressor Proteins (metabolism)