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.