The cerebrospinal-fluid soluble form of Alzheimer's amyloid beta is complexed to SP-40,40 (apolipoprotein J), an inhibitor of the complement membrane-attack complex.
The amyloid fibrils deposited in Alzheimer's neuritic plaque cores and cerebral blood vessels are mainly composed of aggregated forms of a unique peptide, 39-42 amino acids long, named amyloid beta (A beta). A similar, although soluble, A beta ('sA beta') has been identified in cerebrospinal fluid, plasma and cell supernatants, indicating that it is normally produced by proteolytic processing of its precursor protein, amyloid precursor protein (APP). Using direct binding experiments we have isolated and characterized an 80 kDa circulating protein that specifically interacts with a synthetic peptide identical with A beta. The protein was unmistakably identified as SP-40,40 or ApoJ, a cytolytic inhibitor and lipid carrier, by means of amino acid sequence and immunoreactivity with specific antibodies. Immunoprecipitation with anti-SP-40,40 retrieved soluble A beta from cerebrospinal fluid, indicating that the interaction occurs in vivo.
Ghiso
J
J
Department of Pathology, New York University Medical Center, NY 10016.
Matsubara
E
E
Koudinov
A
A
Choi-Miura
N H
NH
Tomita
M
M
Wisniewski
T
T
Frangione
B
B
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002846:Chromatography, Affinity; D051152:Clusterin; D015938:Complement Membrane Attack Complex; D004591:Electrophoresis, Polyacrylamide Gel; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D012995:Solubility
D016229:Amyloid beta-Peptides; C495242:CLU protein, human; D051152:Clusterin; D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; D018832:Molecular Chaperones