Investigations into the protective actions of CBD in the early synaptic deficits in dementia

Accumulation of hyper-phosphorylated tau is a key event in Alzheimer’s disease (AD). Aberrant changes in tau cause synaptic abnormalities and cognitive deficits in early AD. Consequently limiting the aberrant effects of tau on synaptic function may prevent the synaptic abnormalities underlying AD-related cognitive deficits. Cannabinoids are known to have protective actions in the CNS, and recent evidence supports a role for cannabidiol (CBD) in the protective actions. However, we have limited knowledge of whether CBD has the ability to prevent the aberrant effects of tau at synapses that occur in AD. Here we propose to explore this using cell-based models that mirror tau-related synaptic dysfunction, and a combination of electrophysiology, immunocytochemistry and confocal microscopy to monitor effects on hippocampal excitatory synaptic transmission and glutamate receptor trafficking. The therapeutic potential of CBD will be addressed by assessing effects on the synaptic targeting of tau and related hippocampal synaptic impairments, in tau models and P301L transgenic mice. To assess if CBD alleviates tau-linked memory deficits we will use behavioural assays to measure hippocampal-dependent memory in P301L mice. This study will greatly increase our understanding of tau-related synaptic abnormalities, and it will provide valuable insight into the protective effects of CBD against tau-related synaptic dysfunction.

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