The β-amyloid epitope masking activity in human brain is identified as albumin

Abstract

Human brain homogenate proteins were analyzed for binding and processing activity in relation to brain beta-amyloid precursor protein (APP). The homogenate was purified by arginine-Sepharose 4B affinity chromatography, which traps proteins with affinity to certain groups of arginine residue, such as serine proteases and zymogens. A 69 kDa protein that 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 anti-APP antibodies revealed that the masking activity is complete for beta-amyloid epitope(s), but incomplete for cytoplasmic and extracellular 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 precursor protein and its peptides.