Sialic acid moiety of apolipoprotein E3 at Thr 194 affects its interaction with β-amyloid 1–42 peptides

Abstract

Background The 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. Methods We prepared normal apoE3 and its mutant (Thr 194 → Ala) and analyzed their interactions with Aβ 1–42 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. Results The 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 Aβ 1–42 reduced after neuraminidase treatment. Conclusions We 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.