Specific patterns of amyloid β-protein precursor isoform secretion and proteolysis in cultured human cells

This is the authors' abstract. We don't add key points for this paper.

A characteristic neuropathologic feature of Alzheimer c disease is an abundance of brain-localized neuritic plaques. These plaques are identified as areas of degenerating nerve terminals surrounding cores of aggregated and insoluble fibrils of amyloid β-protein (Aβ). Aβ is generated by proteolytic cleavage of a large precursor protein, the amyloid β-protein precursor (AβPP). In this study, soluble AβPPs (sAβPPs) secreted by human cell lines originating from different tissues were characterized. Various human cell types were shown to secrete different characteristic isoforms of AβPP. Peripheral cells (i.e., fibroblasts and keratinocytes) secreted only the soluble derivative of the 770-amino acid isoform (sAβPP770). In contrast, cells derived from the central and peripheral nervous system (i.e., neumblastoma and glioblastoma) secreted the soluble derivative of the 751-amino acid isoform (sAβPP751), while the 695-amino acid isoform (sAβPP695) was secreted exclusively by neuronal-type cells. We have also detected proteolysis of both sAβPP751 and sAβPP770 that results in cleavage of the amide bond at Arg301-Ala302. This bond is located within the reactive center of the Kunitz protease inhibitor (KPI) domain of the sAβPP751 and sAβPP770 isoforms, which suggests that this proteolytic event is associated with a distinct catabolic pathway for the KPI-containing AβPP isoforms.