Selective Loss of KGDHC-Enriched Neurons in Alzheimer Temporal Cortex

Abstract

The Research Objective 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 spring 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. Methods. We examined by immunohistochemistry the cellular distribution of a mitochondrial constituent (the α-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. Results. 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 (ppSignificance. 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.