Sialic acid moiety of apolipoprotein E3 at Thr(194) affects its interaction with beta-amyloid(1-42) peptides.
BACKGROUND
The interaction between apolipoprotein (apo) E and beta-amyloid (Abeta) 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-Abeta interaction.


METHODS
We prepared normal apoE3 and its mutant (Thr(194) --> Ala) and analyzed their interactions with Abeta(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 Abeta(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.
Sugano
Mitsutoshi
M
Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Japan.
Yamauchi
Kazuyoshi
K
Kawasaki
Kenji
K
Tozuka
Minoru
M
Fujita
Kiyotaka
K
Okumura
Nobuo
N
Ota
Hiroyoshi
H
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D053318:Apolipoprotein E3 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007700:Kinetics; D008081:Liposomes; D009154:Mutation / Q000235:genetics; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009439:Neuraminidase / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D011485:Protein Binding; D020349:Surface Plasmon Resonance; D013912:Threonine / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D053318:Apolipoprotein E3; D008081:Liposomes; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D013912:Threonine; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid