The aggregation of the β-amyloid protein Aβ(1-42) plays a fundamental rolein the pathogenesis of Alzheimer´s disease (AD) that is closely linked toneuronal toxicity. It has been described that Aβ(1-42) interacts withgangliosides with a certain affinity. The accumulation of GM1gangliosidecomplexes with Aβ(1-42) has been reported in brains of patients with AD.Previous studies indicate that both the oligosaccharide portion and thehydrophobic portion of the GM1 participate in the interaction. In order todiscern the participation of the oligosaccharide portion, we synthesized newmolecules containing only the oligosaccharide portion of GM1 ganglioside(called osGM1) or covalently linked to chitosan, a biocompatible cationicpolymer (osGM1-Ch ganglioside like-glycan cluster molecules). This nanoparticlewas synthesized by using low molecular weight chitosan (MW~ 100 kD) loaded with1 µmol osGM1/1.28 mg of chitosan. We have tested the effect of these newmolecules against GM1 micelles.

We used β-lactoglobulin (β-lg)  as amyloid-like aggregation model.Benzy alcohol induce amyloid fibers Thio T positive (a fluorescent marker ofamyloid fibers) in β-lg in aqueous buffer at physiologic pH.  We have alsoused synthetic Aβ(1-42) peptide.   

Preliminary results showed that osGM1 has no practically effect on β-lginduced, fibers, GM1 and acidic GM1-H+  micelles have a slightdisaggregating effect whereas osGM1-Ch enhances its effect. Over preformedAβ(1-42) fibers in  aqueous solution, osGM1 prevents or delays the timedepending self-disaggregating amyloid fibers. Instead, nanoparticle osGM1-Chhas a marked disaggregating effect over preformed Aβ(1-42) fibers but similareffect was also obtained by non-loaded carrier chitosan. Additional experimentsare still necessary to attribute some property to the oligosaccharide part ofthe GM1 ganglioside in its aggregating-disaggregating effect in in-vitroexperimental models of amyloids.