NEURONAL CELL-DEATH IN ALZHEIMERS-DISEASE CORRELATES WITH APOE UPTAKEAND INTRACELLULAR A-BETA STABILIZATION

The brains of individuals with Alzheimer's disease (AD) are characteri zed by extracellular deposition of beta-amyloid protein (A beta), intr acellular neurofibrillary tangles, and loss of neurons, To study molec ular markers associated with dying cells in the AD brain, in situ DNA labeling techniques were used to visualize cells with DNA fragmentatio n, We observed that intracellular accumulation of apolipoprotein E (ap oE) is correlated with the detection of intracellular A beta-like immu noreactivity within the same cytoplasmic granules, suggesting that upt ake of lipids may have stabilized the hydrophobic A beta protein withi n the cell. These apoE-containing neurons also exhibit high expression of a cell surface receptor, gp330, which is known to bind apoE, Cells containing significant nuclear DNA fragmentation express the highest level of cell surface gp330, Extracellular deposition of A beta is det ected only upon neuronal cell death, initially as halos of A beta immu noreactivity around individual dying neurons, and subsequently as A be ta plaques containing numerous neuronal cell ghosts, Based on our in s itu analysis of nuclear DNA fragmentation, we conclude that neuronal c ell death likely occurs before the extracellular deposition of A beta in AD brains.