Production of the Alzheimer amyloid beta protein by normal proteolytic processing.
The 4-kilodalton (39 to 43 amino acids) amyloid beta protein (beta AP), which is deposited as amyloid in the brains of patients with Alzheimer's diseases, is derived from a large protein, the amyloid beta protein precursor (beta APP). Human mononuclear leukemic (K562) cells expressing a beta AP-bearing, carboxyl-terminal beta APP derivative released significant amounts of a soluble 4-kilodalton beta APP derivative essentially identical to the beta AP deposited in Alzheimer's disease. Human neuroblastoma (M17) cells transfected with constructs expressing full-length beta APP and M17 cells expressing only endogenous beta APP also released soluble 4-kilodalton beta AP, and a similar, if not identical, fragment was readily detected in cerebrospinal fluid from individuals with Alzheimer's disease and normal individuals. Thus cells normally produce and release soluble 4-kilodalton beta AP that is essentially identical to the 4-kilodalton beta AP deposited as insoluble amyloid fibrils in Alzheimer's disease.
Shoji
M
M
Department of Neurology, Gunma University, Japan.
Golde
T E
TE
Ghiso
J
J
Cheung
T T
TT
Estus
S
S
Shaffer
L M
LM
Cai
X D
XD
McKay
D M
DM
Tintner
R
R
Frangione
B
B
D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015151:Immunoblotting; D007951:Leukemia, Myeloid / Q000378:metabolism*; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000378:metabolism*; D014162:Transfection
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor