title: Chromosomal DNA damage measured using the cytokinesis-block micronucleus cytome assay is significantly associated with cognitive impairment in South Australians.
abstract: Loss of genome integrity may be associated with increased risk for neurodegenerative disease. The aim of this study was to investigate whether mild cognitive impairment (MCI) or Alzheimer's disease (AD) individuals have increased DNA damage relative to age- and gender- matched controls using the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. DNA damage was measured as micronuclei (MN), nucleoplasmic bridges (NPB), and nuclear buds (NBUD) in binucleated cells. The assay was performed on blood samples from 80 participants consisting of (i) MCI cases (N = 20) and age- and gender- matched controls (N = 20), and (ii) AD cases (N = 20) and age- and gender- matched controls (N = 20). There was a significant increase in MCI NBUD frequency (P = 0.006) relative to controls, which was also observed in male (P = 0.03) and female (P = 0.04) subgroups. For AD cases, there were no significant differences in assay biomarkers relative to controls. There was a significant negative correlation between Mini Mental State Examination (MMSE) and (i) MN in all controls, (R = -0.3, P = 0.04), and AD cases (R = -0.4, P = 0.03), (ii) NPB in all controls, (R = -0.4, P = 0.006) and AD cases (R = -0.5, P = 0.01), and (iii) NBUD in MCI cases (R = -0.5, P = 0.007) and AD cases (R = -0.7, P = 0.0002). The results suggest that an increase in lymphocyte CBMN-Cyt DNA damage biomarkers may be associated with cognitive decline.
authors.affiliation: Commonwealth Scientific and Industrial Research Organisation (Animal, Food, and Health Sciences), Adelaide, South Australia; Discipline of Physiology, School of Medical Sciences, The University of Adelaide, Adelaide, South Australia.
authors.forename: Sau Lai
authors.initials: SL
authors.lastname: Lee
authors.forename: Philip
authors.initials: P
authors.lastname: Thomas
authors.forename: Jane
authors.initials: J
authors.lastname: Hecker
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Faunt
authors.forename: Michael
authors.initials: M
authors.lastname: Fenech
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics; D001315:Australia; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000235:genetics; D002877:Chromosomes, Human / Q000235:genetics*; D060825:Cognitive Dysfunction / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D003430:Cross-Sectional Studies; D048749:Cytokinesis / Q000235:genetics; D004249:DNA Damage / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D015162:Micronucleus Tests / Q000379:methods*; D008875:Middle Aged
chemical_list: D015415:Biomarkers
keywords: Alzheimer's disease; DNA damage; cytokinesis-block micronucleus cytome assay; mild cognitive impairment