Liposomes functionalized with GT1b ganglioside with high affinity for amyloid beta-peptide

Alzheimer's Disease (AD) is a neurodegenerative disorder that affects millions of individuals worldwide. Accumulation of amyloid-peptide (A beta) in the brain, and its aggregation into oligomers, fibrils and plaques, plays a central role in the onset and development of AD. Starting from this observation, the E.C. FP7 project "NAD" (Nanoparticles for therapy and diagnosis of Alzheimer's disease) is involved in the design of nanoparticles that recognize and remove brain All Previous investigations by NAD Consortium have already produced nanoparticles containing anionic phospholipids or curcumin-analogues able to bind A beta with very high affinity, to inhibit fibril formation and to reduce A beta toxicity in-vitro. Starting from the observation that ganglioside GT1b binds A beta in vitro, we have synthesized liposomes, composed of sphingomyelin and cholesterol and containing GT1b ganglioside, and investigated their affinity towards A beta peptide. Surface Plasmon Resonance experiments showed a good interaction of liposomes with A beta fibrils, displaying Kd values between 125 and 150 nM. Moreover, A beta aggregation into fibrils, measured by Thioflavin T and Congo Red binding assays, was reduced of about 50%, after two weeks of monomeric peptide incubation in the presence of GT1b-containing liposomes. The ability of GT1b-containing liposomes, and the other liposomes previously described by NAD research, to bind A beta and to reduce fibrils formation, increases the interest in studying them as possible future diagnostic and therapeutic tools for the treatment of Alzheimer Disease