The frequency of point mutations in mitochondrial DNA is elevated in the Alzheimer's brain

Using a PCR-based strategy, we found that point mutation frequencies in mit ochondrial DNA (mtDNA)were 2- to 3-fold higher in the parietal gyrus, hippo campus, and cerebellum from subjects with Alzheimer's disease (AD) compared to normal controls. In contrast, levels of a commonly studied deletion mut ation, mtDNA(4977), were not elevated in AD. The frequency of point mutatio ns did not vary significantly among the three brain areas, whereas the freq uency of mtDNA(4977) was 15- to 25-fold lower in the cerebellum in comparis on to the cortex; this regional variation was seen in both the normal and A lzheimer's brain. In blood mtDNA, point mutation frequencies were not eleva ted in AD patients. The elevated frequency of point mutations in all three brain regions is consistent with the idea that increased oxidant stress is associated with AD, (C) 2000 Academic Press.