High density lipoprotein decreases β-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 (Aβ) protein, within the brain. It has been postulated that Aβ may in some way contribute directly to AD pathogenesis. The ε4 allele of apolipoprotein E (apoE) is a major AD risk factor. Since both apoE and Aβ are components of lipoproteins in plasma and cerebrospinal fluid, we asked whether lipoproteins and apoE isoforms would modify the toxicity of Aβ(1-42) in cortical cell cultures. We show that high density lipoprotein with or without apoE reduces Aβ toxicity and that apoE in the absence of lipoproteins does not affect Aβ toxicity. These results suggest that interactions between Aβ and lipoproteins in the brain could influence AD pathogenesis.