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Updated: Jul 18, 2026

Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain
Published on: August 28, 2012
Processing of the amyloid protein precursor to potentially amyloidogenic derivatives
T E Golde1, S Estus, L H Younkin
1Division of Neuropathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106.
Abstract:
The approximately 120-kilodalton amyloid beta protein precursor (beta APP) is processed into a complex set of 8- to 12-kilodalton carboxyl-terminal derivatives that includes potentially amyloidogenic forms with the approximately 4-kilodalton amyloid beta protein (beta AP) at or near their amino terminus. In order to determine if these derivatives are processed in a secretory pathway or by the endosomal-lysosomal system, (i) deletion mutants that produce the normal set of carboxyl-terminal derivatives and shortened secreted derivatives were analyzed and (ii) the effect of inhibitors of endosomal-lysosomal processing was examined. In the secretory pathway, cleavage of the beta APP occurs at a single site within the beta AP to generate one secreted derivative and one nonamyloidogenic carboxyl-terminal fragment, whereas, in the endosomal-lysosomal system, a complex set of carboxyl-terminal derivatives is produced that includes the potentially amyloidogenic forms.
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