DNA strand breaks in Alzheimer's disease

The goal of this study was to investigate the presence of DNA damage in Alz heimer's disease (AD) utilizing independent assays for three different type s of DNA strand breaks. Sections from hippocampi of AD brains, brains with Alzheimer neurofibrillary changes (Ch) from non-demented individuals, and c ontrols (C) were labeled with (1) the TUNEL assay to identify blunt-ended a nd 3' protruding termini of breaks in double-stranded DNA, (2) the Klenow a ssay 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 detecte d in AD, followed by Ch, and controls (C). Zn either AD and Ch, the inciden ce of TUNEL- or Klenow-positive nuclei did not differ significantly, but wa s higher than the incidence of Apostain-positive nuclei. With all three ass ays, 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 Apost ain assay, the product of the labeling reaction was localized either to the periphery of the nucleus or to distinct clumps of chromatin (or both). Wit h the TUNEL assay, the majority of positive nuclei were diffusely labeled. In both AD and Ch, the individual positive nuclei were labeled with both th e Klenow and the TUNEL assays. The results indicate high incidence of nucle i with either double-stranded or single-stranded DNA breaks in AD, which, f or the forms detectable with the Klenow or TUNEL assays, were colocalized. (C) 1999 Elsevier Science B.V. All rights reserved.