Mitochondrial enzyme-deficient hippocampal neurons and choroidal cells in AD

Objective: To determine whether hippocampal neurons and choroidal epithelia l cells demonstrate a mitochondrial enzyme deficiency in AD more frequently than in normal aging. Background: High levels of mutant mitochondrial DNA (mtDNA) cause a deficiency in cytochrome c oxidase (COX) (complex IV activi ty) because three of its 13 subunits are encoded for by mtDNA. In contrast, succinate dehydrogenase (SDH) (complex II activity) remains intact because all of its subunits are nuclear encoded. The histologic hallmark of cells containing high levels of mtDNA mutation in both primary mtDNA disorders an d normal aging muscle is the presence of COX-deficient SDH-positive cells. Methods: The authors applied a sequential histochemical method for COX and SDH to hippocampal sections in 17 AD and 17 age-matched control brains. Thi s confers the advantages of both looking at individual cells in situ and me asuring the actual mitochondrial complex activity rather than simply the co mplex quantity. Results: COX-deficient SDH-positive hippocampal neurons and choroidal epithelial cells are more prevalent in patients with AD than in controls. In addition the COX-deficient SDH-positive choroidal cells are as sociated with an enlargement in size. Conclusion: This increase in number o f COX-deficient SDH-positive hippocampal pyramidal neurons and choroid epit helial cells provides strong evidence that a substantial mitochondrial enzy me activity defect occurs in individual cells more frequently in AD than in normal aging and that mitochondria may play a significant role in the path ogenesis of AD.