Cytoplasmic cytochrome c immunolabelling in dystrophic neurites in Alzheimer's disease

• Published in: Acta neuropathologica Vol. 112; no. 4; pp. 429 - 437
• Main Authors: Woodhouse, Adele, Vickers, James C, Dickson, Tracey C
• Format: Journal Article
• Language: English
• Published: Germany Springer Nature B.V 01.10.2006
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Apoptosis; Brain research; Cytochrome; Cytochromes c - metabolism; Dementia; Female; Humans; Immunohistochemistry; Labeling; Localization; Male; Medical research; Neocortex - metabolism; Neocortex - pathology; Neocortex - ultrastructure; Neoplasm Proteins - metabolism; Neurites - metabolism; Neurites - pathology; Neurofilament Proteins - metabolism; Neurons - metabolism; Neurons - pathology; Neurons - ultrastructure; Pathology; Pneumonia; Proteins; tau Proteins - metabolism
• ISSN: 0001-6322; 1432-0533
• DOI: 10.1007/s00401-006-0107-3

Cytochrome c has a well-established role in electron transfer and as a mediator of apoptotic cell death. The cortical and intracellular localisation of cytochrome c immunoreactivity was examined in Alzheimer's disease and control cases. No differences in the cortical labelling pattern or the density of cytochrome c-positive cells in neocortical layer V were present between control and Alzheimer's disease cases. Punctate cytochrome c labelling was present in a subset of neocortical neurons, including clusters of intensely labelled pyramidal neurons that were not specifically associated with beta-amyloid plaques. With respect to Alzheimer's disease associated pathology, only 6.7 +/- 1.4% of neurons showing neurofibrillary tangle formation demonstrated punctate cytochrome c immunoreactivity. These results suggest that cytochrome c may label a subset of pyramidal neurons that is susceptible, yet relatively resistant, to Alzheimer's disease pathology. A low percentage of neurofilament triplet protein medium, tau and chromogranin A labelled dystrophic neurites were also cytochrome c-positive. There was also a trend towards an increase in the percentage of cytochrome c immunoreactive dystrophic neurites in pathologically aged control cases compared to Alzheimer's disease cases, suggesting that cytochrome c may be an early and transient epitope within dystrophic neurites. In contrast to the punctate cytochrome c labelling observed in cortical cells, cytoplasmic cytochrome c labelling was observed within dystrophic neurites. Although cytochrome c release is indicative of the activation of the intrinsic apoptotic pathway, cytoplasmic cytochrome c may also indicate mitochondrial damage or dysfunction.