Marked changes in mitochondrial DNA deletion levels in Alzheimer brains.
Levels of the common 4977 nucleotide pair (np) mitochondrial DNA (mtDNA) deletion (mtDNA4977) were quantitated in the cortex, putamen, and cerebellum of patients with Alzheimer disease (AD) and compared to age-matched controls. Although cerebellum deletion levels were comparably low in AD patients and controls of all ages, cortical deletion levels were clearly different. The levels of mtDNA deletions in control brains started low, but rose markedly after age 75, while those of AD patients started high and declined to low levels by age 80. Choosing age 75 to arbitrarily delineate between younger and older subjects, younger patients had 15 times more mtDNA deletions than younger controls, while older patients had one-fifth the deletion level of older controls. Younger AD patients also had fourfold more deletions than older AD patients. These results support the hypothesis that OXPHOS defects resulting from somatic mtDNA mutations may play a role in AD pathophysiology.
Department of Genetics and Molecular Medicine, Emory University School of Medicine, Atlanta, Georgia 30322.
M
M
Corral-Debrinski
T
T
Horton
M T
MT
Lott
J M
JM
Shoffner
A C
AC
McKee
M F
MF
Beal
B H
BH
Graham
D C
DC
Wallace
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010085:Oxidative Phosphorylation; D011699:Putamen / Q000378:metabolism; D017384:Sequence Deletion; D014018:Tissue Distribution
D004272:DNA, Mitochondrial