Amyloid β Binds to Albumin-Associated Lrp-Like Plasma O-Glycoproteins: Albumin Prevents Inhibition of Binding by LDL

• Published in: Protein and peptide letters Vol. 26; no. 11; p. 869
• Main Authors: Karthi, Sreedevi, Sumitha, K C, Geetha, Mandagini, Appukuttan, Padinjaradath S
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2019
• Subjects: anti-β-glucoside antibody; LRP; albumin-associated-O-glycosylated protein; Anti-α-galactoside antibody; amyloid β; serine- and threonine-rich peptide sequence
• ISSN: 1875-5305
• DOI: 10.2174/0929866526666190722151027

Albumin was reported to engage nearly 95% of plasma Amyloid β (Aβ) and to reverse Aβ fibril formation in brain. Since O-glycosylated LRP family of receptors capture Aβ in brain we compared Aβ binding to electrophoretically purified albumin and to O-glycoproteins AOP1 and AOP2 that adhere noncovalently to plasma albumin. Strength of Aβ-protein interaction was measured as fluorescence increase in Fluorescentlabeled Aβ (F-Aβ) resulting from conformational changes. Alternatively, differential segregation of free and protein-bound Aβ in Density Gradient Ultracentrifugation (DGUC) was also examined. Fluorescence enhancement in F-Aβ was significantly greater by AOP1 and AOP2 than by known Aβ reactants α -synuclein and β -cyclodextrin, but nil by albumin. In DGUC Aβ migrated with the O-glycoproteins but not with albumin. Free O-glycoproteins unlike their albumin-bound forms were blocked by LDL from capturing F-Aβ. Associated albumin did not affect Aβ binding of O-glycoproteins. De-O-glycosylation of AOP1/AOP2 enhanced their Aβ binding showing that peptide sequences at O-glycosylated regions were recognized by Aβ. Unlike albumin, AOP1 and AOP2 were immunologically cross-reactive with LRP. Albumin sample used earlier to report albumin-Aβ interaction contained two O-glycoproteins cross-reactive with human LRP and equal in size to human AOP1 or AOP2. Unlike albumin, albumin-bound O-glycoproteins, immunologically cross-reactive with LRP, bind plasma Aβ. These O-glycoproteins are potential anti-amyloidogenic therapeutics if they inhibit Aβ aggregation as other Aβ reactants do. Circulating immune complexes of albuminbound O-glycoproteins with O-glycoprotein-specific natural antibodies can bind further to LRP-like membrane proteins and are possible O-glycoprotein transporters to tissues.