engleski

Absence of apoptosis but increased DNA fragmentation in subregions of the Alzheimer hippocampus: Relationship to patterns of cell loss and nNOS immunoreactivity

We studied patterns of neuronal degeneration in systematically sampled serial sections through hippocampi of 2 control and 4 confirmed Alzheimer (AD) patients. As clear cell loss is found in the AD hippocampus (3), we first assessed distribution of DNA fragmentation and necrotic/apoptotic cell death using in situ end labeling (ISEL) through the complete rostrocaudal length of the hippocampus. Second, we investigated whether there was a relationship between ISEL and the immunocytochemically identified neuronal form of nitric oxide synthase (nNOS) in adjacent sections (4). With ISEL, mainly CA1 and hilar, and sometimes subicular areas were labeled, showing large numbers of ISEL-positive, necrotic neurons and many positive (micro)glia-like cells. In the dentate gyrus, only very occassionally was labeling observed, whereas surrounding cortical areas showed no labeling, suggesting a strong anatomical preference of the pathological changes for the hippocampal area. No clear preference over the rostro-caudal axis was observed. In controls, ISEL labeling was virtually absent. In agreement with earlier studies (1, 2) but in contrast to others (5, 6), no apoptotic, but only necrotic morphology of neurons was observed in AD. nNOS staining in adjacent sections was prominent in CA3 and CA2 regions, areas showing hardly any ISEL-positive cells. Our results confirm now in a systematically sampled series through the entire hippocampus, that: a) increased DNA vulnerability is present in AD, b) phagocytosis of fragmented DNA appears to occur, by microglia-like cells, and c) the enhanced level of hippocampal DNA fragmentation in AD is not anatomically related to nNOS expression in neurons, which agrees with the proposed role for nNOS in neuronal resistance to degeneration. (1) Lucassen et al., J Neuropathol Exp Neurol 1997 ; 56:887-900 (2) Stadelmann et al., J Neuropathol Exp Neurol 1998 ; in press (3) Simic et al., J Comp Neurol 1997 ; 379:484-492 (4) Simic et al., Soc Neurosci Abst 1997 ; #1641.2 (5) Anderson et al., J Neurosci 1996 ; 16:1710-1719 (6) Smale et al., Exp Neurol 1995 ; 133:225-230

Alzheimer's disease; astrocytes; brain nitric oxide synthase; DNA damage; entorhinal cortex; hippocampus; immunocytochemistry; in situ end labeling

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