Production of the Alzheimer amyloid β protein by normal proteolytic processing

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

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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.

Original languageEnglish (US)
Pages (from-to)126-129
Number of pages4
JournalScience
Volume258
Issue number5079
DOIs
StatePublished - Jan 1 1992

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Cite this

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 β protein by normal proteolytic processing. Science, 258(5079), 126-129. https://doi.org/10.1126/science.1439760