Selective loss of KGDHC-enriched neurons in Alzheimer temporal cortex: does mitochondrial variation contribute to selective vulnerability?

of this study was to test whether variation in mitochondrial composition is associated with "selective vulnerability" in Alzheimer brain. The term "selective vulnerability" refers to the loss of relatively vulnerable brain cells and the sparing of relatively resistant brain cells...

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Bibliographic Details
Published in:Journal of molecular neuroscience 2001-12, Vol.17 (3), p.361-369
Main Authors: Ko, L W, Sheu, K F, Thaler, H T, Markesbery, W R, Blass, J P
Format: Article
Language:English
Subjects:
Aged
Alzheimer Disease - enzymology
Alzheimer Disease - pathology
Autopsy
Biopsy
Brain
Cell Count
Cell Death
Female
Glial Fibrillary Acidic Protein - analysis
Humans
Immunohistochemistry
Ketoglutarate Dehydrogenase Complex - analysis
Ketoglutarate Dehydrogenase Complex - immunology
Male
Middle Aged
Mitochondria
Mitochondria - enzymology
Neurons
Neurons - enzymology
Phosphopyruvate Hydratase - analysis
Temporal Lobe - enzymology
Temporal Lobe - pathology
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Summary:of this study was to test whether variation in mitochondrial composition is associated with "selective vulnerability" in Alzheimer brain. The term "selective vulnerability" refers to the loss of relatively vulnerable brain cells and the sparing of relatively resistant brain cells in disorders in which a genetic defect or environmental agent acts on both types of cells. The mechanisms underlying selective vulnerability are largely unknown, but mitochondria may be involved; the composition of mitochondria varies among different types of neurons, and mitochondria have an important role in cell death. Alzheimer's Disease (AD) is one of a number of neurodegenerative disorders in which both selective vulnerability and abnormalities of mitochondria occur. We examined by immunohistochemistry the cellular distribution of a mitochondrial constituent (the alpha-ketoglutarate dehydrogenase complex, KGDHC) known to be deficient in AD, in relation to the known selective vulnerability of neurons in areas 21 and 22 of the temporal lobe in this neurodegenerative disorder. In normal human brain, cortical layers III and V contain neurons intensely immunoreactive for KGDHC, compared to other cells in these areas. The KGDHC-enriched cells are lost in AD (p < 0.001). In layer III, the loss of KGDHC-enriched cells is proportional to total loss of neurons, as determined by immunoreactivity to neuron specific enolase (NSE). In layer V, a higher proportion of the KGDHC-enriched neurons are lost than of other (NSE positive) neurons (p < 0.001). Variations in mitochondrial composition may be one of the factors determining which cells die first when different types of cells are exposed to the same stress.
ISSN:0895-8696
1559-1166
DOI:10.1385/JMN:17:3:361