Production of the Alzheimer Amyloid β Protein by Normal Proteolytic Processing
SciencePublished 2 October 1992
Mikio Shoji, Todd E. Golde, Jorge Ghiso, Tobun T. Cheung, Steven Estus, Lillian M. Shaffer
Citations1,445
SJR quartileQ1
SJR score10.42
SNIP6.62
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TL;DR
Human mononuclear leukemic cells expressing a beta AP-bearing, carboxyl-terminal beta APP derivative released significant amounts of a soluble 4-kilodalton beta AP derivative essentially identical to the beta AP deposited in Alzheimer's disease.
Abstract
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.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
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