Soluble derivatives of the beta amyloid protein precursor of Alzheimer's disease are labeled by antisera to the beta amyloid protein.
The amyloid deposited in Alzheimer's disease (AD) is composed primarily of a 39-42 residue polypeptide (beta AP) that is derived from a larger beta amyloid protein precursor (beta APP). In previous studies, we and others identified full-length, membrane-associated forms of the beta APP and showed that these forms are processed into soluble derivatives that lack the carboxyl-terminus of the full-length forms. In this report, we demonstrate that the soluble approximately 125 and approximately 105 kDa forms of the beta APP found in human cerebrospinal fluid are specifically labeled by several different antisera to the beta AP. This finding indicates that both soluble derivatives contain all or part of the beta AP sequence, and it suggests that one or both of these forms may be the immediate precursor of the amyloid deposited in AD.
Palmert
M R
MR
Division of Neuropathology, Case Western Reserve University School of Medicine, Cleveland OH 44106.
Siedlak
S L
SL
Podlisny
M B
MB
Greenberg
B
B
Shelton
E R
ER
Chan
H W
HW
Usiak
M
M
Selkoe
D J
DJ
Perry
G
G
Younkin
S G
SG
D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000378:metabolism*; D000595:Amino Acid Sequence; D000682:Amyloid / Q000032:analysis* / Q000096:biosynthesis* / Q000134:cerebrospinal fluid / Q000276:immunology; D016564:Amyloid beta-Protein Precursor; D001921:Brain / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D000939:Epitopes / Q000032:analysis; D006801:Humans; D007106:Immune Sera; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D011480:Protease Inhibitors / Q000032:analysis; D011498:Protein Precursors / Q000032:analysis* / Q000134:cerebrospinal fluid / Q000276:immunology
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D000939:Epitopes; D007106:Immune Sera; D008565:Membrane Proteins; D009842:Oligopeptides; D011480:Protease Inhibitors; D011498:Protein Precursors