Sialic acid moiety of apolipoprotein E3 at Thr194 affects its interaction with β-amyloid1–42 peptides

BackgroundThe interaction between apolipoprotein (apo) E and β-amyloid (Aβ) is associated with the development of Alzheimer's disease (AD); however, the details remain unknown. ApoE in cerebrospinal fluid is extensively sialylated, and sialylation of certain proteins are known to modulate biological function. We investigated the effects of a sialic acid moiety of apoE on the apoE–Aβ interaction.MethodsWe prepared normal apoE3 and its mutant (Thr194 → Ala) and analyzed their interactions with Aβ1–42 by using the surface plasmon resonance (SPR) assay. In addition, we performed the SPR assay by using apoE-containing lipoproteins treated with neuraminidase. We also assessed the effect of the mutation on the interaction of apoE3 with liposomes.ResultsThe binding avidity of the mutant apoE3# was approximately 50% that of normal apoE3 (p < 0.0001). The binding avidity of the apoE-containing lipoproteins for Aβ1–42 reduced after neuraminidase treatment.ConclusionsWe suggest that AD development is controlled not only by the apoE isoforms but also by the posttranslational modifications in apoE, such as those in the sialic acid moieties, which are abundant in apoE derived from the brain.