ELEVATED LEVELS OF THE KEARNS-SAYRE SYNDROME MITOCHONDRIAL-DNA DELETION IN TEMPORAL CORTEX OF ALZHEIMERS PATIENTS

A mitochondrial hypothesis of Alzheimer's disease (AD) has been propos ed based on a number of studies which establish altered oxidative phos phorylation (OXPHOS) and ATP synthesis in AD tissue. Four out of five complexes in the OXPHOS pathway are partly encoded by mitochondrial DN A (mtDNA); thus, this may be a crucial site of lesions that alter brai n activity. We examined temporal cortex autopsy tissue for deleted mtD NA 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 effect s by Southern analysis, no evidence of mtDNA degradation after 30 h of postmortem delay at room temperature was found. Nine tissue samples t aken 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 K earns-Sayre syndrome. Using this method we determined that AD temporal cortex had a 6.5-fold greater frequency of mtDNA(Delta 4977) than con trols (0.0593% vs. 0.0092%, p = 0.0269, one-tailed; p = 0.0530, two-ta iled), indicating that damaged mtDNA preferentially accumulates in AD compared to aged brain. (C) 1997 Elsevier Science B.V.