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Lookup NU author(s): Dr David Cottrell, Dr Theresa Wardell, Emeritus Professor Doug Turnbull, Dr Margaret Johnson
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Mitochondrial abnormalities, in particular the accumulation of mitochondrial DNA mutations, have been proposed as a potential cause of normal ageing. One group of patients with mtDNA disorders have a nuclear DNA defect which accelerates the chronological accumulation of mitochondrial DNA mutations. These patients provide an ideal means of investigating whether accelerated mitochondrial DNA defects can cause accelerated ageing pathology. The choroid plexus demonstrates a robust accumulation of pathological changes, in the form of Biondi bodies, with normal ageing. We have therefore examined the choroid plexus of a case with multiple mitochondrial DNA deletions for evidence of accelerated ageing and compared it with two cases with point mutation mitochondrial DNA disorders and several age-matched and elderly controls with and without clinical and neuropathological evidence of neurodegenerative disease. We also demonstrate that the choroid plexus of the mitochondrial DNA cases contain cells with levels of mitochondrial DNA mutation sufficient to cause a biochemical deficiency in the oxidative phosphorylation pathway. As previously reported, both cases with point mutation mitochondrial DNA disorders exhibit a characteristic oncocytic type transformation of the choroidal epithelial cells. However, in the case with multiple mitochondrial DNA deletions we demonstrate pathological changes in choroid plexus that are strongly suggestive of accelerated ageing. We believe that this finding supports the theory that the accumulation of mitochondrial DNA mutations can lead to pathological changes typical of ageing cells.
Author(s): Cottrell DA, Ince PG, Wardell TM, Turnbull DM, Johnson MA
Publication type: Article
Publication status: Published
Journal: Neuropathology and Applied Neurobiology
Year: 2001
Volume: 27
Issue: 3
Pages: 206-214
ISSN (print): 0305-1846
ISSN (electronic): 1365-2990
Publisher: Wiley-Blackwell
URL: http://dx.doi.org/10.1046/j.1365-2990.2001.00315.x
DOI: 10.1046/j.1365-2990.2001.00315.x
PubMed id: 11489140
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