Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive decline, motor impairments, and accumulation of hallmark proteins, amyloid-beta (Aβ) and tau. Traditionally, transgenic mouse models for AD have focused on Aβ pathology, however, recently a number of tauopathy transgenic models have been developed, including the TAU58/2 transgenic model. Cannabidiol (CBD), a non-toxic constituent of the Cannabis sativa plant, has been shown to prevent and reverse cognitive deficits in Aβ transgenic mouse models of AD. Importantly, the therapeutic properties of CBD on the behavioural phenotype of tauopathy mouse models have not been investigated.

We assessed the impact of chronic CBD treatment (i.e. 50 mg/kg CBD i.p. administration starting 3 weeks prior to behavioural assessments) on disease-relevant behaviours of 4-month-old TAU58/2 transgenic males in paradigms for anxiety, motor functions, and cognition.

TAU58/2 transgenic males demonstrated reduced body weight, anxiety and impaired motor functions. Furthermore, they demonstrated increased freezing in fear conditioning compared to wild type-like animals. Interestingly, both sociability and social recognition memory were intact in AD transgenic mice. Chronic CBD treatment did not affect behavioural changes in transgenic males.

In summary, 4-month-old TAU58/2 transgenic males exhibited no deficits in social recognition memory, suggesting that motor deficits and changes in anxiety at this age do not impact on social domains. The moderate increase in fear-associated memory needs further investigation but could be related to differences in fear extinction. Future investigations will need to clarify CBD's therapeutic potential for reversing motor deficits in TAU58/2 transgenic mice by considering alternative CBD treatment designs including changed CBD dosing.

阿尔茨海默氏病（AD）是一种神经退行性疾病，其特征是进行性认知能力下降，运动障碍以及标志性蛋白质，β-淀粉样蛋白（Aβ）和tau积累。传统上，用于AD的转基因小鼠模型集中于Aβ病理学，但是，最近已经开发出许多tauopathy转基因模型，包括TAU58 / 2转基因模型。大麻二酚（CBD）是大麻植物的无毒成分，已显示出可以预防和逆转AD的Aβ转基因小鼠模型中的认知缺陷。重要的是，尚未研究CBD对tauopathy小鼠模型的行为表型的治疗特性。

我们评估了慢性CBD治疗（即在行为评估前3周开始ip腹膜内给药50 mg / kg CBD）对4个月大的TAU58 / 2转基因男性的焦虑，运动功能和范式与疾病相关行为的影响认识。

TAU58 / 2转基因男性表现出减轻的体重，焦虑和运动功能受损。此外，与野生型动物相比，他们表现出在恐惧条件下的冰冻增加。有趣的是，在AD转基因小鼠中，社交能力和社交识别记忆均完好无损。慢性CBD治疗不影响转基因男性的行为变化。

总之，4个月大的TAU58 / 2转基因男性在社交识别记忆方面没有表现出缺陷，这表明在这个年龄段，运动功能缺陷和焦虑的改变不会影响社交领域。恐惧相关记忆的适度增加需要进一步调查，但可能与恐惧消退的差异有关。未来的研究将需要通过考虑替代性CBD治疗设计（包括改变CBD剂量）来阐明CBD在TAU58 / 2转基因小鼠中逆转运动缺陷的治疗潜力。