Clusterin Inhibits A Beta(42) Aggregation Through A "Strawberry Model" As Detected By Fret-Fcs

Extracellular plaque deposits of beta-amyloid peptide (A beta) are one of the main pathological features of Alzheimer's disease (AD), The aggregation of A beta(42) species, especially A beta(42) oligomers, is still an active research field in AD pathogenesis. Secretory clusterin protein (sCLU), an extracellular chaperone, plays an important role in AD pathogenesis. Although sCLU interacts directly with A beta(42) in vitro and in vivo, the mechanism is not clear. In this paper, His-tagged sCLU (sCLU-His) was cloned, expressed and purified, and we applied florescence resonance energy transfer-fluorescence correlation spectroscopy (FRET-FCS) to investigate the direct interaction of sCLU-His and A beta(42) at the single-molecule fluorescence level in vitro. Here, we chose four different fluorescently labeled A beta(42) oligomers to form two different groups of aggregation models, easy or difficult to aggregate. The results showed that sCLU-His could form complexes with both aggregation models, and sCLU-His inhibited the aggregation of A beta(42/RB) similar to A beta(42/Atto647) (easy to aggregate model). The complexes were produced as the A beta(42/Label) adhered to the sCLU-His, which is similar to a "strawberry model," as strawberry seeds are dotted on the outer surface of strawberries. This work provided additional insight into the interaction mechanism of sCLU and A beta(42).