THE SOLUBLE FORM OF ALZHEIMERS AMYLOID-BETA PROTEIN IS COMPLEXED TO HIGH-DENSITY-LIPOPROTEIN-3 AND VERY HIGH-DENSITY-LIPOPROTEIN IN NORMAL HUMAN PLASMA

The amyloid fibrils of Alzheimer's neuritic plaques and cerebral blood vessels are mainly composed of aggregated forms of a 39 to 44 amino a cids peptide, named amyloid beta (A beta). A similar although soluble form of A beta (sA beta) has been identified in plasma, cerebrospinal fluid and cell culture supernatants, indicating that it is produced un der physiologic conditions. We report here that sA beta in normal huma n plasma is associated with lipoprotein particles, in particular to th e HDL(3) and VHDL fractions where it is complexed to ApoJ and, to a le sser extent, to ApoAl. This was assessed by immunoprecipitation experi ments of purified plasma lipoproteins and lipoprotein-depleted plasma and confirmed by means of amino acid sequence analysis. Moreover, biot inylated synthetic peptide A beta(1-40) was traced in normal human pla sma in in vitro experiments. As in the case of sA beta, biotinylated A beta(1-40) was specifically recovered in the HDL(3) and VHDL fraction s. This data together with the previous demonstration that A beta(1-40 ) is taken up into the brain via a specific mechanism and possibly as an A beta(1-40)-ApoJ complex indicate a role for HDL(3)- and VHDL-cont aining ApoJ in the transport of the peptide in circulation and suggest their involvement in the delivery of sA beta across the blood-brain b arrier. (C) 1994 Academic Press, Inc.