A hallmark of Alzheimer's disease (AD) is the extracellular deposition
and accumulation of a 39-43 amino peptide, known as the amyloid beta
(A beta) protein, within the brain. It has been postulated that A beta
may in some way contribute directly to AD pathogenesis. The epsilon 4
allele of apolipoprotein E (apoE) is a major AD risk factor. Since bo
th apoE and A are components of lipoproteins in plasma and cerebrospin
al fluid, we asked whether lipoproteins and apoE isoforms would modify
the toxicity of A beta(1-42) in cortical cell cultures. We show that
high density lipoprotein with or without apoE reduces A beta toxicity
and that apoE in the absence of lipoproteins does not affect A beta to
xicity. These results suggest that interactions between A beta and lip
oproteins in the brain could influence AD pathogenesis.