MARKED CHANGES IN MITOCHONDRIAL-DNA DELETION LEVELS IN ALZHEIMER BRAINS

Levels of the common 4977 nucleotide pair (np) mitochondrial DNA (mtDN A) deletion (mtDNA(4977)) were quantitated in the cortex, putamen, and cerebellum of patients with Alzheimer disease (AD) and compared to ag e-matched controls. Although cerebellum deletion levels were comparabl y low in AD patients and controls of all ages, cortical deletion level s were clearly different. The levels of mtDNA deletions in control bra ins started low, but rose markedly after age 75, while those of AD pat ients started high and declined to low levels by age 80. Choosing age 75 to arbitrarily delineate between younger and older subjects, younge r patients had 15 times more mtDNA deletions than younger controls, wh ile older patients had one-fifth the deletion level of older controls. Younger AD patients also had fourfold more deletions than older AD pa tients. These results support the hypothesis that OXPHOS defects resul ting from somatic mtDNA mutations may play a role in AD pathophysiolog y. (C) 1994 Academic Press, Inc.