DNA strand breaks in Alzheimer's disease.
The goal of this study was to investigate the presence of DNA damage in Alzheimer's disease (AD) utilizing independent assays for three different types of DNA strand breaks. Sections from hippocampi of AD brains, brains with Alzheimer neurofibrillary changes (Ch) from non-demented individuals, and controls (C) were labeled with (1) the TUNEL assay to identify blunt-ended and 3' protruding termini of breaks in double-stranded DNA, (2) the Klenow assay to detect single-stranded and double-stranded breaks with protruding 5' termini, and (3) the Apostain assay which utilizes a monoclonal antibody to single-stranded DNA and is based on the decreased stability of apoptotic DNA to thermal denaturation caused by DNA breaks. The highest incidence of nuclei positive for either molecular form of DNA strand breaks was detected in AD, followed by Ch, and controls (C). In either AD and Ch, the incidence of TUNEL- or Klenow-positive nuclei did not differ significantly, but was higher than the incidence of Apostain-positive nuclei. With all three assays, the highest incidence of positive nuclei was in the molecular layer of CA1. In the majority of nuclei positive for either the Klenow or the Apostain assay, the product of the labeling reaction was localized either to the periphery of the nucleus or to distinct clumps of chromatin (or both). With the TUNEL assay, the majority of positive nuclei were diffusely labeled. In both AD and Ch, the individual positive nuclei were labeled with both the Klenow and the TUNEL assays. The results indicate high incidence of nuclei with either double-stranded or single-stranded DNA breaks in AD, which, for the forms detectable with the Klenow or TUNEL assays, were colocalized.
Adamec
E
E
Mailman Research Center, McLean Hospital, 115 Mill Street, Belmont, MA, USA. eadamec@mercury.mclean.org
Vonsattel
J P
JP
Nixon
R A
RA
D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D017209:Apoptosis; D004249:DNA Damage; D018891:Dentate Gyrus / Q000473:pathology; D006624:Hippocampus / Q000166:cytology / Q000473:pathology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D018613:Microscopy, Confocal; D016874:Neurofibrillary Tangles / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000473:pathology; D017966:Pyramidal Cells / Q000166:cytology / Q000473:pathology; D012016:Reference Values