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.