Multiple inhibitory effects of Alzheimer's peptide A beta 1-40 on lipid biosynthesis in cultured human HepG2 cells

Herein we describe the inhibitory effect of the synthetic peptide A beta 1-40, homologous to the major high-density lipoprotein-associated species of Alzheimer's amyloid beta protein (A beta), on lipid biosynthesis in human hepatic HepG2 cells. This culture synthesizes various lipids from [C-14]acetate as a precursor. Treatment of cells with different concentrations of A beta 1-40 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 mere free and esterified cholesterol and phospholipids. This inhibitory effect suggests that A beta 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.