EVIDENCE FOR APOPTOTIC CELL-DEATH IN ALZHEIMERS-DISEASE

We provide evidence for apoptosis in Alzheimer's disease using the in situ labeling technique TUNEL (terminal transferase-mediated dUTP-biot in nick end labeling). The technique specifically detects apoptotic ce lls by utilizing terminal transferase to incorporate biotinylated nucl eotides into the fragmented DNA of apoptotic cells. The labeled cells are visualized by reaction with avidin peroxidase and a suitable subst rate. Sections from the hippocampus of Alzheimer-diseased (AD) brains and non-AD brains were examined for apoptosis. While considerable vari ation in the quantity of apoptotic cells was observed among individual samples, the incidence of apoptosis in AD brains was elevated in comp arison to age-matched, non-AD brains in specific regions of the hippoc ampal formation. Immunostaining indicated that both neurons and astroc ytes were undergoing apoptosis, although the majority of the TUNEL-pos itive cells appeared to be glial, based on the location of the stained cells. These data suggest that apoptosis may be involved in both the primary neuronal cell loss and in the glial response that is a compone nt of AD. (C) 1995 Academic Press, Inc.