Self-oligomerization of NACP, the precursor protein of the non-amyloid β/A4 protein (Aβ) component of Alzheimer's disease amyloid, observed in the presence of a C-terminal Aβ fragment (residues 25–35)

Abstract

NACP, the precursor protein of the non-amyloid β/A4 protein (Aβ) component of Alzheimer's disease (AD) amyloid, also known as α-synuclein, was suggested to seed amyloid plaque formation in AD by stimulating Aβ aggregation. We have demonstrated that NACP experienced self-oligomerization only in the presence of a modified Aβ fragment (Aβ25–35) by using dicyclohexylcarbodiimide. This NACP oligomerization, appearing as a discrete ladder on a Tricine SDS-PAGE, was not observed with other Aβ peptides such as the reverse peptide Aβ35–25 and Aβ1–40, indicating this process was specific not only for the C-terminal peptide sequence of the Aβ but also for its orientation. It might be, therefore, suggested that the NACP self-oligomers formed only in the presence of a N-terminally truncated Aβ peptide could act as a nucleation center for plaque formation during AD development.