The Soluble Form of Alzheimer′s Amyloid β Protein Is Complexed to High Density Lipoprotein 3 and Very High Density Lipoprotein in Normal Human Plasma

Abstract

The amyloid fibrils of Alzheimer′s neuritic plaques and cerebral blood vessels are mainly composed of aggregated forms of a 39 to 44 amino acids peptide, named amyloid beta (Aβ). A similar although soluble form of Aβ (sAβ) has been identified in plasma, cerebrospinal fluid and cell culture supernatants, indicating that it is produced under physiologic conditions. We report here that sAβ in normal human plasma is associated with lipoprotein particles, in particular to the HDL3 and VHDL fractions where it is complexed to ApoJ and, to a lesser extent, to ApoAl. This was assessed by immunoprecipitation experiments of purified plasma lipoproteins and lipoprotein-depleted plasma and confirmed by means of amino acid sequence analysis. Moreover, biotinylated synthetic peptide Aβ1-40 was traced in normal human plasma in in vitro experiments. As in the case of sAβ, biotinylated Aβ1-40 was specifically recovered in the HDL3 and VHDL fractions. This data together with the previous demonstration that Aβ1-40 is taken up into the brain via a specific mechanism and possibly as an A1-40-ApoJ complex indicate a role for HDL3- and VHDL-containing ApoJ in the transport of the peptide in circulation and suggest their involvement in the delivery of sAβ across the blood-brain barrier. © 1994 Academic Press. All rights reserved.