Oxidative DNA damage in peripheral leukocytes of mild cognitive impairment and AD patients.
It is well established that oxidative stress plays a key role in the degenerative neuronal death and progression of Alzheimer's disease (AD), although it is not clear if it is the primary triggering event in the pathogenesis of this disorder. Mild cognitive impairment (MCI) is a clinical condition between normal aging and AD, characterized by a memory deficit without loss of general cognitive and functional abilities. We performed this study by a comet assay analysis to evaluate the level of primary and oxidative DNA damage in two groups of MCI and AD patients, compared to healthy controls. Data showed a significantly higher level of primary DNA damage in leukocytes of AD and also of MCI patients compared to control individuals (average: 2.09+/-0.79 and 2.47+/-1.01, respectively for AD and MCI, versus 1.04+/-0.31 in controls). Moreover, the amount of oxidised DNA bases (both purines and pyrimidines) was significatively higher in the two groups of patients (AD and MCI) compared to controls. Our results give a further indication that oxidative stress, at least at the DNA level, is an earlier event in the pathogenesis of AD.
Migliore
L
L
Department of Human and Environmental Sciences, University of Pisa, Via S. Giuseppe 22, 56126 Pisa, Italy. I.migliore@geog.unipi.it
Fontana
I
I
Trippi
F
F
Colognato
R
R
Coppedè
F
F
Tognoni
G
G
Nucciarone
B
B
Siciliano
G
G
D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D020552:Comet Assay / Q000379:methods; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology*; D043382:DNA-Formamidopyrimidine Glycosylase; D003839:Deoxyadenosines; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004586:Electrophoresis; D029968:Escherichia coli Proteins; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000473:pathology*; D008875:Middle Aged; D018384:Oxidative Stress; D011687:Purines / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism
C436623:8-hydroxy-2'-deoxyadenosine; D003839:Deoxyadenosines; D029968:Escherichia coli Proteins; D011687:Purines; D011743:Pyrimidines; D043224:Deoxyribonuclease (Pyrimidine Dimer); C106403:NTH protein, E coli; D043382:DNA-Formamidopyrimidine Glycosylase