The beta-amyloid epitope masking activity in human brain is identified as albumin.
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.
Matsumoto
A
A
Department of Radiation Biophysics and Genetics, Kobe University School of Medicine, Japan.
Minami
M
M
Matsumoto
R
R
D000368:Aged; D000418:Albumins / Q000737:chemistry*; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry*; D015153:Blotting, Western; D001923:Brain Chemistry / Q000502:physiology*; D002846:Chromatography, Affinity; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000737:chemistry
D000418:Albumins; D016564:Amyloid beta-Protein Precursor; D000939:Epitopes; D009419:Nerve Tissue Proteins