Elevated levels of the Kearns-Sayre syndrome mitochondrial DNA deletion in temporal cortex of Alzheimer's patients.
A mitochondrial hypothesis of Alzheimer's disease (AD) has been proposed based on a number of studies which establish altered oxidative phosphorylation (OXPHOS) and ATP synthesis in AD tissue. Four out of five complexes in the OXPHOS pathway are partly encoded by mitochondrial DNA (mtDNA); thus, this may be a crucial site of lesions that alter brain activity. We examined temporal cortex autopsy tissue for deleted mtDNA by PCR-based methods and Southern analysis. AD tissue was obtained from autopsy-confirmed cases that had a postmortem delay ranging from 5 to 27 h. Using a rat brain model system to examine postmortem effects by Southern analysis, no evidence of mtDNA degradation after 30 h of postmortem delay at room temperature was found. Nine tissue samples taken from AD autopsy brain (average age 68 years) and nine age-matched controls (average age 66 years) were assessed by serial dilution PCR for the 5 kb deletion (mtDNA delta 4977) previously associated with Kearns-Sayre syndrome. Using this method we determined that AD temporal cortex had a 6.5-fold greater frequency of mtDNA delta 4977 than controls (0.0593% vs. 0.0092%, p = 0.0269, one-tailed; p = 0.0530, two-tailed), indicating that damaged mtDNA preferentially accumulates in AD compared to aged brain.
Hamblet
N S
NS
Department of Biochemistry, Eastern Virginia Medical School, Norfolk 23507-1696, USA.
Castora
F J
FJ
D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D000818:Animals; D004272:DNA, Mitochondrial / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007625:Kearns-Sayre Syndrome / Q000235:genetics*; D008875:Middle Aged; D010085:Oxidative Phosphorylation; D016133:Polymerase Chain Reaction / Q000379:methods; D011180:Postmortem Changes; D051381:Rats; D017207:Rats, Sprague-Dawley; D017384:Sequence Deletion / Q000235:genetics*; D013702:Temporal Lobe / Q000737:chemistry*; D013997:Time Factors
D004272:DNA, Mitochondrial