THE CEREBROSPINAL-FLUID SOLUBLE FORM OF ALZHEIMERS AMYLOID-BETA IS COMPLEXED TO SP-40,40 (APOLIPOPROTEIN-J), AN INHIBITOR OF THE COMPLEMENTMEMBRANE-ATTACK COMPLEX

The amyloid fibrils deposited in Alzheimer's neuritic plaque cores and cerebral blood vessels are mainly composed of aggregated forms of a u nique peptide, 39-42 amino acids long, named amyloid beta (Abeta). A s imilar, although soluble, Abeta ('sAbeta') has been identified in cere brospinal fluid, plasma and cell supernatants, indicating that it is n ormally produced by proteolytic processing of its precursor protein, a myloid precursor protein (APP). Using direct binding experiments we ha ve isolated and characterized an 80 kDa circulating protein that speci fically interacts with a synthetic peptide identical with Abeta. The p rotein was unmistakably identified as SP-40,40 or ApoJ, a cytolytic in hibitor and lipid carrier, by means of amino acid sequence and immunor eactivity with specific antibodies. Immunoprecipitation with anti-SP-4 0,40 retrieved soluble Abeta from cerebrospinal fluid, indicating that the interaction occurs in vivo.