The Interplay of Apoes with Syndecans in Influencing Key Cellular Events of Amyloid Pathology

Apolipoprotein E (ApoE) isoforms exert intricate effects on cellular physiology beyond lipid transport and metabolism. ApoEs influence the onset of Alzheimer’s disease (AD) in an isoform-dependent manner: ApoE4 increases AD risk, while ApoE2 decreases it. Previously we demonstrated that syndecans, a transmembrane proteoglycan family with increased expression AD, trigger aggregation modulate uptake amyloid beta (Aβ). Utilizing our previously established syndecan-overexpressing assays, now explore how interplay syndecans contributes to key events, namely aggregation, Aβ pathology. The interaction indicates isoform-specific characteristics arising frequently studied ApoE–heparan sulfate interactions. Syndecans, among them neuronal syndecan-3, ApoEs, especially ApoE3, exerted opposing syndecan-3-mediated aggregation. internalization monomeric Aβ, hence preventing its extracellular decreased it, thus helping buildup plaques. contrary remained once aggregated: reduced aggregates, facilitated Fibrillation studies also revealed ApoE4′s tendency form fibrillar aggregates. Our results uncover yet unknown details ApoE biology deepen molecular understanding ApoE-dependent mechanism