Multiple inhibitory effects of Alzheimer's peptide Aβ1-40 on lipid biosynthesis in cultured human HepG2 cells

Herein we describe the inhibitory effect of the synthetic peptide Aβ1-40, homologous to the major high-density lipoprotein-associated species of Alzheimer's amyloid P protein (Aβ), on lipid biosynthesis in human hepatic HepG2 cells. This culture synthesizes various lipids from [14C]acetate as a precursor. Treatment of cells with different concentrations of Aβ1-40 decreased the syntheses of various radiolabeled lipid species. The decrease reached saturation at peptide concentrations equal to 10-100 ng ml-1. The lipids whose synthesis was decreased most were free and esterified cholesterol and phospholipids. This inhibitory effect suggests that Aβ protein may modulate physiological intracellular lipid syntheses. It may also be of special importance in the pathological condition, and contribute to the neurodegeneration, in Alzheimer's disease and related disorders.