Mitochondrial DNA Rearrangement Spectrum in Brain Tissue of Alzheimer's Disease: Analysis of 13 Cases.
BACKGROUND
Mitochondrial dysfunction may play a central role in the pathologic process of Alzheimer's disease (AD), but there is still a scarcity of data that directly links the pathology of AD with the alteration of mitochondrial DNA. This study aimed to provide a comprehensive assessment of mtDNA rearrangement events in AD brain tissue.


METHODS
Postmortem frozen human brain cerebral cortex samples were obtained from the Banner Sun Health Research Institute Brain and Body Donation Program, Sun City, AZ. Mitochondria were isolated and direct sequence by using MiSeq®, and analyzed by relative software.


RESULTS
Three types of mitochondrial DNA (mtDNA) rearrangements have been seen in post mortem human brain tissue from patients with AD and age matched control. These observed rearrangements include a deletion, F-type rearrangement, and R-type rearrangement. We detected a high level of mtDNA rearrangement in brain tissue from cognitively normal subjects, as well as the patients with Alzheimer's disease (AD). The rate of rearrangements was calculated by dividing the number of positive rearrangements by the coverage depth. The rearrangement rate was significantly higher in AD brain tissue than in control brain tissue (17.9%versus 6.7%; p = 0.0052). Of specific types of rearrangement, deletions were markedly increased in AD (9.2% versus 2.3%; p = 0.0005).


CONCLUSIONS
Our data showed that failure of mitochondrial DNA in AD brain might be important etiology of AD pathology.
Neurology Department, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.|Pediatric Department, University of Illinois at Chicago, Peoria, United States of America.
Yucai
Y
Chen
SoftGenetics LLC, State College, United States of America.
Changsheng
C
Liu
Pediatric Department, University of Illinois at Chicago, Peoria, United States of America.
William Davis
WD
Parker
Pediatric Department, University of Illinois at Chicago, Peoria, United States of America.
Hongyi
H
Chen
Banner Sun Health Research Institute, Sun City, United States of America.
Thomas G
TG
Beach
SoftGenetics LLC, State College, United States of America.
Xinhua
X
Liu
Banner Sun Health Research Institute, Sun City, United States of America.
Geidy E
GE
Serrano
Neurology Department, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Yanfen
Y
Lu
Neurology Department, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Jianjun
J
Huang
Neurology Department, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Kunfang
K
Yang
Neurology Department, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Chunmei
C
Wang
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004272:DNA, Mitochondrial / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000473:pathology; D020641:Polymorphism, Single Nucleotide
D004272:DNA, Mitochondrial