Ganglioside GQ1b ameliorates cognitive impairments in an Alzheimer's disease mouse model, and causes reduction of amyloid precursor protein

Brain-derived neurotrophic factor (BDNF) plays crucial roles in memory impairments including Alzheimer's disease (AD). Previous studies have reported that tetrasialoganglioside GQ1b is involved in long-term potentiation and cognitive functions as well as BDNF expression. However, in vitro and in vivo functions of GQ1b against AD has not investigated yet. Consequently, treatment of oligomeric A beta followed by GQ1b significantly restores A beta(1-42)induced cell death through BDNF up-regulation in primary cortical neurons. Bilateral infusion of GQ1b into the hippocampus ameliorates cognitive deficits in the triple-transgenic AD mouse model (3xTg-AD). GQ1b-infused 3xTg-AD mice had substantially increased BDNF levels compared with artificial cerebrospinal fluid (aCSF)-treated 3xTg-AD mice. Interestingly, we also found that GQ1b administration into hippocampus of 3xTg-AD mice reduces A beta plaque deposition and tau phosphorylation, which correlate with APP protein reduction and phospho-GSK3 beta level increase, respectively. These findings demonstrate that the tetrasialoganglioside GQ1b may contribute to a potential strategy of AD treatment.