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Abstract
Background: Alzheimer s disease (AD) is the most prevalent form of dementia, characterised by amyloid-β (Aβ) plaques and neurofibrillary tangles. Other processes include neurodegeneration, neuroinflammation, neurotoxicity and oxidative stress. Patients suffer from widespread behavioural and cognitive decline, including social withdrawal and memory loss. Therapeutic options are limited and efficacy is poor, prompting the need for other potential therapeutic avenues. In particular, emerging studies implicate the non-psychoactive phytocannabinoid, cannabidiol (CBD), as a potential therapeutic option due to its anti-inflammatory, antioxidant and neuroprotective properties that may be relevant for AD. In vitro evidence shows CBD prevents Aβ-induced neurotoxicity, neuroinflammation, cell death, tau protein hyperphosphorylation and promotes adult hippocampal neurogenesis.
Method: The aim of my thesis was to evaluate the therapeutic potential of CBD in a genetic mouse model of AD. I established novel behavioural phenotypes including social recognition and spatial memory deficits for the APPSwe/PS1∆E9 (APPxPS1) double transgenic mouse model and determined the in vivo effects of CBD treatment on AD mice. For this, I assessed the ability of CBD to remedy or prevent the development of cognitive deficits and brain pathophysiology of APPxPS1 mice by daily treatment with either vehicle or CBD (20 mg/kg) for: a) 3 weeks post-onset (intraperitoneal administration), or b) 8 months (oral administration) prior to the onset of AD. Treatment was followed by comprehensive cognitive testing and AD-relevant biochemical analyses.
Results: APPxPS1 mice exhibited cognitive deficits in spatial memory and social recognition. CBD treatment prevented and reversed recognition memory deficits of APPxPS1 transgenic mice. Biochemical analyses implicated that the therapeutic potential of CBD might be related to its impact on neuroinflammation and dietary phytosterols.
Conclusions: APPxPS1 transgenic mice demonstrated novel cognitive deficits relevant for AD. These deficits could be prevented and ameliorated by CBD treatment potentially via its anti-inflammatory actions and its impact on dietary phytosterols. CBD possesses therapeutic potential for the treatment of AD symptomatology and should be evaluated further in clinical trials.