title: Mitochondrial DNA deletions cause the biochemical defect observed in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is the most common form of dementia, increasing in prevalence with age. Most patients who develop AD have an unknown cause, but characteristic neuropathological features include the deposition of extracellular amyloid beta and of intraneuronal hyperphosphorylated tau protein. Researchers have previously implicated mitochondrial dysfunction in AD. We previously showed an increase in neurons displaying a mitochondrial biochemical defect-cytochrome-c oxidase (COX) deficiency-in the hippocampus in patients with sporadic AD compared with age-matched controls. COX deficiency is well described as a marker of mitochondrial (mt) DNA dysfunction. This present study analyzed the mtDNA in single neurons from both COX normal and COX-deficient cells. Analysis of the mtDNA revealed that COX deficiency is caused by high levels of mtDNA deletions which accumulate with age. Future research is needed to clarify the role mtDNA deletions have in normal aging and investigate the relationship between mtDNA deletions and the pathogenesis of sporadic AD.
authors.affiliation: Centre for Brain Ageing and Vitality, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK. k.j.krishnan@ncl.ac.uk
authors.forename: Kim J
authors.initials: KJ
authors.lastname: Krishnan
authors.forename: Thiloka E
authors.initials: TE
authors.lastname: Ratnaike
authors.forename: Heidi L M
authors.initials: HL
authors.lastname: De Gruyter
authors.forename: Evelyn
authors.initials: E
authors.lastname: Jaros
authors.forename: Doug M
authors.initials: DM
authors.lastname: Turnbull
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics*; D016022:Case-Control Studies; D030401:Cytochrome-c Oxidase Deficiency / Q000209:etiology / Q000235:genetics / Q000473:pathology; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000473:pathology; D009245:NADH Dehydrogenase / Q000235:genetics; D009474:Neurons / Q000201:enzymology*; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D003576:Electron Transport Complex IV; D009245:NADH Dehydrogenase; D012333:RNA, Messenger; C098483:NADH dehydrogenase subunit 4; C515075:NADH dehydrogenase subunit 1, human