The beta-amyloid protein precursor of Alzheimer disease has soluble derivatives found in human brain and cerebrospinal fluid.
In this study, we use antisera to synthetic beta-amyloid protein precursor (beta APP) peptides to identify, in human brain and cerebrospinal fluid (CSF), soluble approximately 125- and approximately 105-kDa derivatives of the beta APP that lack the carboxyl terminus of the full-length, membrane-associated forms. We show that the soluble approximately 125-kDa beta APP derivative contains the Kunitz protease inhibitor domain, whereas the approximately 105-kDa form does not, and we confirm that these two proteins are soluble beta APP derivatives by purifying each from human CSF and directly sequencing its amino terminus.
Palmert
M R
MR
Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106.
Podlisny
M B
MB
Witker
D S
DS
Oltersdorf
T
T
Younkin
L H
LH
Selkoe
D J
DJ
Younkin
S G
SG
D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000378:metabolism*; D000595:Amino Acid Sequence; D000682:Amyloid / Q000138:chemical synthesis / Q000235:genetics / Q000302:isolation & purification*; D016564:Amyloid beta-Protein Precursor; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D006801:Humans; D007106:Immune Sera; D015151:Immunoblotting; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011498:Protein Precursors / Q000138:chemical synthesis / Q000235:genetics / Q000302:isolation & purification*; D014162:Transfection
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D007106:Immune Sera; D011498:Protein Precursors