Cell surface proteoglycan-mediated uptake and accumulation of the Alzheimer's disease peptide Aβ(1–42)

Publication date: Available online 23 August 2018Source: Biochimica et Biophysica Acta (BBA) - BiomembranesAuthor(s): Emelie Wesén, Audrey Gallud, Alexandra Paul, David J. Lindberg, Per Malmberg, Elin K. EsbjörnerAbstractProteoglycans (PGs) have been found in Alzheimer's disease amyloid-β (Aβ) plaques and their glycosaminoglycan chains reportedly influence Aβ aggregation, neurotoxicity and intracellular accumulation in cell and animal models, but their exact pathophysiological role(s) remain unclear. We have studied the cellular uptake of fluorescently labelled Aβ(1–42) and Aβ(1–40) peptides in normal CHO cells (K1) and the mutant cell line (pgsA-745) which lacks all protein-attached heparan and chondroitin sulfate chains. After 24 h of incubation, CHO-K1 accumulates more Aβ(1–42) and Aβ(1–40) compared with CHO-pgsA-745, consistent with the suggested role of PGs in Aβ uptake. However, after short incubation times (≤3 h) there was no difference; moreover, the time evolution of Aβ(1–42) accumulation in CHO-K1 followed an unusual sigmoidal-like trend, indicating a possible involvement of PG-mediated peptide aggregation in Aβ endocytosis. Neither Aβ(1–42) nor Aβ(1–40) could stimulate uptake of a dextran (a general endocytosis marker) suggesting that Aβ-induced endocytosis upregulation does not occur. CHO-K1 cells contained a higher number of Aβ(1–42)-positive vesicles, whereas the intensity difference per vesicle was only marginal suggesting ...
Source: Biochimica et Biophysica Acta (BBA) Biomembranes - Category: Biochemistry Source Type: research