The soluble form of Alzheimer's 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 acids 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 under physiologic conditions. We report here that sA beta 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 ApoAI. 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 A beta 1-40 was traced in normal human plasma in in vitro experiments. As in the case of sA beta, biotinylated A beta 1-40 was specifically recovered in the HDL3 and VHDL fractions. 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 HDL3- and VHDL-containing ApoJ in the transport of the peptide in circulation and suggest their involvement in the delivery of sA beta across the blood-brain barrier.
Koudinov
A
A
Department of Pathology, New York University Medical Center, NY 10016.
Matsubara
E
E
Frangione
B
B
Ghiso
J
J
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000097:blood* / Q000302:isolation & purification; D000906:Antibodies; D002499:Centrifugation, Density Gradient; D002851:Chromatography, High Pressure Liquid; D051152:Clusterin; D004591:Electrophoresis, Polyacrylamide Gel; D006023:Glycoproteins / Q000097:blood / Q000302:isolation & purification; D006801:Humans; D015151:Immunoblotting; D008075:Lipoproteins, HDL / Q000097:blood* / Q000302:isolation & purification; D053440:Lipoproteins, HDL3; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis; D011485:Protein Binding; D012016:Reference Values; D012995:Solubility
D016229:Amyloid beta-Peptides; D000906:Antibodies; C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; D018832:Molecular Chaperones; D010455:Peptides; C026277:very high density lipoproteins