Title:Amyloid β Binds to Albumin-Associated Lrp-Like Plasma O-Glycoproteins: Albumin Prevents Inhibition of Binding by LDL
VOLUME: 26 ISSUE: 11
Author(s):Sreedevi Karthi, K. C. Sumitha, Mandagini Geetha and Padinjaradath S. Appukuttan*
Affiliation:Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 695011, Kerala, Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 695011, Kerala, Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 695011, Kerala, Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 695011, Kerala
Keywords:Anti-α-galactoside antibody, anti-β-glucoside antibody, albumin-associated-O-glycosylated protein, amyloid β,
serine- and threonine-rich peptide sequence, LRP.
Abstract:
Background: Albumin was reported to engage nearly 95% of plasma Amyloid β (Aβ)
and to reverse Aβ fibril formation in brain.
Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
