Orally administered selenium-containing α-D-1,6-glucan and α-D-1,6-glucan relief early cognitive deficit in APP/PS1 mice

Alzheimer's disease (AD) is a complex, progressive and deadly disorder that exhibits various typical pathological characteristics. Till now no effective treatment has been found that can prevent or reverse AD. Here, the effects of 2 months of treatment with α-D-1,6-glucan (CPA) and selenium-containing α-D-1,6-glucan (Se-CPA) on early cognitive dysfunction and neuropathology were explored in the 3-month-old APP/PS1 transgenic mouse. The results of the Morris water maze and open-field test revealed that Se-CPA exerted more significant effects than CPA in improving cognitive function and depressive-like behavior by attenuating the oxidative stress, decreasing serum LPS level, downregulating the inflammation of astrocytes and microglia through inhibiting the activation of NLRP3 inflammasome, mitigating neuronal cells loss and improving synaptic plasticity. Moreover, Se-CPA exerted beneficial effects on reshaping gut microbiome by increasing the microbial α-diversity, enhancing the proportion of beneficial bacteria such as Akkermansia muciniphila and promoting the SCFAs concentration. These findings provide evidence that Se-CPA might be a potentially viable compound for AD prevention.