A mitochondrial DNA deletion in normally aging and in Alzheimer brain tissue.
By quantitative polymerase chain reaction (PCR) of total cellular DNA, the known 4977 bp deletion in human mitochondrial DNA (mtDNA delta 4977) was not detected in rapidly dividing tissue such as placenta and lymphocytes, nor in brain tissue from fetuses and in frontal cortex from two individuals 24 and 56 years old. However, in frontal cortex from individuals 71-95 years 0.13% deleted/undeleted mtDNA was found, with no significant difference between Alzheimer patients (0.14%) and age-matched controls (0.12%). We hypothesize that the age-related accumulation of this deletion (and other expected deletions) contributes to the down-regulation of adenosine triphosphate (ATP) production in neurons and other non-dividing cells, a fundamental mechanism common to aging and Alzheimer's disease.
Blanchard
B J
BJ
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Park
T
T
Fripp
W J
WJ
Lerman
L S
LS
Ingram
V M
VM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D001923:Brain Chemistry / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D015183:Restriction Mapping; D017384:Sequence Deletion / Q000502:physiology*
D004272:DNA, Mitochondrial; D009841:Oligonucleotides