Accelerated ageing changes in the choroid plexus of a case with multiple mitochondrial DNA deletions

Mitochondrial abnormalities, in particular the accumulation of mitochondria l 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 choro id plexus demonstrates a robust accumulation of pathological changes, in th e form of Biondi bodies, with normal ageing. We have therefore examined the choroid plexus of a case with multiple mitochondrial DNA deletions for evi dence of accelerated ageing and compared it with two cases with point mutat ion mitochondrial DNA disorders and several age-matched and elderly control s with and without clinical and neuropathological evidence of neurodegenera tive disease. We also demonstrate that the choroid plexus of the mitochondr ial DNA cases contain cells with levels of mitochondrial DNA mutation suffi cient to cause a biochemical deficiency in the oxidative phosphorylation pa thway. As previously reported, both cases with point mutation mitochondrial DNA disorders exhibit a characteristic oncocytic type transformation of th e choroidal epithelial cells. However, in the case with multiple mitochondr ial DNA deletions we demonstrate pathological changes in choroid plexus tha t are strongly suggestive of accelerated ageing. We believe that this findi ng supports the theory that the accumulation of mitochondrial DNA mutations can lead to pathological changes typical of ageing cells.