High density lipoprotein decreases beta-amyloid toxicity in cortical cell culture.

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 both apoE and A beta are components of lipoproteins in plasma and cerebrospinal 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 toxicity. These results suggest that interactions between A beta and lipoproteins in the brain could influence AD pathogenesis.