SECRETORY FORM OF ALZHEIMER AMYLOID PRECURSOR PROTEIN-695 IN HUMAN BRAIN LACKS BETA-A4 AMYLOID IMMUNOREACTIVITY

It is not clear how Alzheimer amyloid precursor proteins (APP) are metabolized in the brain itself. Secretory forms of APP in a phosphate buffer-soluble traction were purified from post-mortem human brain by heparin-affinity and ion-exchange chromatography and analyzed by N-terminal amino acid sequencing and SDS polyacrylamide gel electrophoresis/immunoblotting. We found apparently similar multi-isoforms of secretory APP (at 93-97, 105-112 and 123 KDa) to those that we have described recently in cerebrospinal fluid. Antisera to the intial part of the β/A4 sequence labelled only those bands that were found to react with antiserum to the Kunitz-type inhibitor insert of APP, suggesting that β/A4 amyloid may be generated specifically from APP-695. © 1993 Academic Press.