THE BETA-AMYLOID EPITOPE MASKING ACTIVITY IN HUMAN BRAIN IS IDENTIFIED AS ALBUMIN

HUMAN brain homogenate proteins were analyzed for binding and processi ng activity in relation to brain beta-amyloid precursor protein (APP). The homogenate was purified by arginine-Sepharose 4B affinity chromat ography, which traps proteins with affinity to certain groups of argin ine residue, such as serine proteases and zymogens. A 69 kDa protein t hat masks epitope(s) of brain APP was found in a weakly bound fraction . The nature of the 69 kDa brain protein was identified as albumin by N-terminal amino acid sequencing and Western blot analysis using anti- human albumin antibody. Western blot analysis with domain-specific ant i-APP antibodies revealed that the masking activity is complete for be ta-amyloid epitope(s), but incomplete for cytoplasmic and extracellula r domain epitopes, suggesting that the interaction site of the albumin is beta-amyloid itself. Therefore, it seems that brain albumin is not merely a carrier protein for beta-amyloid in cerebrospinal fluid, but also a modulator which interferes with processing of beta-amyloid pre cursor protein and its peptides.