Browse by author
Lookup NU author(s): Dr David Cottrell, Dr Margaret Johnson, Emeritus Professor Doug Turnbull
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Objective: To determine whether hippocampal neurons and choroidal epithelial 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 activity) 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 and 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. This confers the advantages of both looking at individual cells in situ and measuring the actual mitochondrial complex activity rather than simply the complex 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 associated with an enlargement in size. Conclusion: This increase in number of COX-deficient SDH-positive hippocampal pyramidal neurons and choroid epithelial cells provides strong evidence that a substantial mitochondrial enzyme activity defect occurs in individual cells more frequently in AD than in normal aging and that mitochondria may play a significant role in the pathogenesis of AD.
Author(s): Cottrell DA; Johnson MA; Turnbull DM; Blakely EL; Ince PG
Publication type: Article
Publication status: Published
Journal: Neurology
Year: 2001
Volume: 57
Issue: 2
Pages: 260-264
ISSN (print): 0028-3878
ISSN (electronic): 1526-632X
Publisher: Lippincott Williams & Wilkins
URL: http://www.neurology.org/content/57/2/260.abstract
PubMed id: 11468310
