, Volume 110, Issue 3, pp 315-316

Alzheimer pathology associated with POLG1 mutation, multiple mtDNA deletions, and APOE4/4: premature ageing or just coincidence?

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Mitochondrial DNA (mtDNA) with multiple deletions accumulate in ageing, which has formed the basis for a theory that mtDNA mutations may play a role in ageing and degenerative disorders, such as Alzheimer’s disease (AD) [1, 6]. Autosomal dominant progressive external ophthalmoplegia (adPEO) represents a group of disorders with nuclear genetic heterogeneity [3] and multiple mtDNA deletions, which are clonally expanded in post-mitotic tissues [4]. To investigate a possible association between multiple mtDNA deletions and AD, we performed post-mortem morphological, immunohistochemical, and mtDNA studies of the brains of two siblings from a Swedish adPEO family. These patients harbored the mtDNA polymerase gamma (POLG1) Y955C mutation [3].

Patient IV.4, previously reported in a Swedish adPEO family [3, 4], died at the age of 60 years. He developed hypokinesia and rigidity at the age of 58. Psychometric tests at age 54 and 57 showed impaired spatial construction ability and short-term memory