DOI: 10.1126/science.1439760. Production of the Alzheimer Amyloid β Protein by Normal Proteolytic Processing

Production of the Alzheimer Amyloid β Protein by Normal Proteolytic Processing

10.1126/science.1439760

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

The 4-kilodalton (39 to 43 amino acids) amyloid β protein (βAP), which is deposited as amyloid in the brains of patients with Alzheimer's disease, is derived from a large protein, the amyloid β protein precursor (βAPP). Human mononuclear leukemic (K562) cells expressing a βAP-bearing, carboxyl-terminal βAPP derivative released significant amounts of a soluble 4-kilodalton βAPP derivative essentially identical to the βAP deposited in Alzheimer's disease. Human neuroblastoma (M17) cells transfected with constructs expressing full-length βAPP and M17 cells expressing only endogenous βAPP also released soluble 4-kilodalton βAP, 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 βAP that is essentially identical to the 4-kilodalton βAP deposited as insoluble amyloid fibrils in Alzheimer's disease.

Bibliography

Shoji, M., Golde, T. E., Ghiso, J., Cheung, T. T., Estus, S., Shaffer, L. M., Cai, X.-D., McKay, D. M., Tintner, R., Frangione, B., & Younkin, S. G. (1992). Production of the Alzheimer Amyloid Î² Protein by Normal Proteolytic Processing. Science, 258(5079), 126â129.

Authors 11

Mikio Shoji (first)
Todd E. Golde (additional)
Jorge Ghiso (additional)
Tobun T. Cheung (additional)
Steven Estus (additional)
Lillian M. Shaffer (additional)
Xiao-Dan Cai (additional)
Deborah M. McKay (additional)
Ron Tintner (additional)
Bias Frangione (additional)
Steven G. Younkin (additional)

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Dates

Type	When
Created	18 years, 10 months ago (Oct. 5, 2006, 7:03 p.m.)
Deposited	1 year, 7 months ago (Jan. 10, 2024, 9:07 p.m.)
Indexed	3 weeks, 1 day ago (Aug. 6, 2025, 8:43 a.m.)
Issued	32 years, 10 months ago (Oct. 2, 1992)
Published	32 years, 10 months ago (Oct. 2, 1992)
Published Print	32 years, 10 months ago (Oct. 2, 1992)

Funders 0

None

BibTeX

@article{Shoji_1992, title={Production of the Alzheimer Amyloid β Protein by Normal Proteolytic Processing}, volume={258}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1439760}, DOI={10.1126/science.1439760}, number={5079}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Shoji, Mikio and Golde, Todd E. and Ghiso, Jorge and Cheung, Tobun T. and Estus, Steven and Shaffer, Lillian M. and Cai, Xiao-Dan and McKay, Deborah M. and Tintner, Ron and Frangione, Bias and Younkin, Steven G.}, year={1992}, month=oct, pages={126–129} }

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