IN-SITU LABELING OF DYING CORTICAL-NEURONS IN NORMAL AGING AND IN ALZHEIMERS-DISEASE - CORRELATIONS WITH SENILE PLAQUES AND DISEASE PROGRESSION

We examined the degeneration of neocortical neurons in normal aging an d Alzheimer's disease (AD) using terminal transferase (TdT)-mediated d eoxyuridine triphosphate (d-UTP)-biotin nick-end labeling (TUNEL), a m ethod that identifies DNA strand breaks and constitutes a positive mar ker for dying neurons. TUNEL was positive in neurons, glia, and microg lial cells in AD but not in younger or age-matched cognitively charact erized controls. Neuronal labeling in AD was most conspicuous in corti cal layer III in the early stages of the disease and became more wides pread as the disease progressed. In addition, we observed TUNEL of lam ina III neurons in a subset of older subjects who had normal cognition but abundant neocortical senile plaques. In concert, the availability of a direct marker of dying neurons allows for specific correlations of cell death with other neuropathological markers as well as clinical variables. Observations from the present study suggest that the death of cortical neurons precedes the symptomatic stage of AD and evolves in parallel with the clinical progression of the disease and that ther e appears to he an association between the degree of cell death and th e severity of senile plaques.