Brain Research ( IF 2.7 ) Pub Date : 2021-07-04 , DOI: 10.1016/j.brainres.2021.147579 Luisa Möhle 1 , Mirjam Brackhan 2 , Pablo Bascuñana 1 , Jens Pahnke 3
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Introduction
Alzheimer’s disease (AD) is the leading cause of dementia and a major global health issue. Currently, only limited treatment options are available to patients. One possibility to expand the treatment repertoire is repurposing of existing drugs such as dimethyl fumarate (DMF). DMF is approved for treatment of multiple sclerosis and previous animal studies have suggested that DMF may also have a beneficial effect for the treatment of AD.
Methods
We used an APPPS1 transgenic model of senile β-amyloidosis and treated female mice orally with DMF in two treatment paradigms (pre and post onset). We quantified learning and memory parameters, β-amyloidosis, and neuroinflammation to determine the potential of DMF as AD therapeutics.
Results
Treatment with DMF had no influence on water maze performance, β-amyloid accumulation, plaque formation, microglia activation, and recruitment of immune cells to the brain. Compared to vehicle-treated animals, oral DMF treatment could not halt or retard disease progression in the mice.
Discussion
Our results do not favour the use of DMF as treatment for AD. While our results stand in contrast to previous findings in other models, they emphasize the importance of animal model selection and suggest further studies to elucidate the mechanisms leading to conflicting results.
中文翻译：
富马酸二甲酯不会减轻雌性 APPPS1 小鼠的认知能力下降和 β-淀粉样变性
介绍
阿尔茨海默病 (AD) 是痴呆症的主要原因，也是全球主要的健康问题。目前，只有有限的治疗选择可供患者使用。扩大治疗范围的一种可能性是重新利用现有药物，例如富马酸二甲酯 (DMF)。DMF 被批准用于治疗多发性硬化症，之前的动物研究表明 DMF 也可能对治疗 AD 具有有益作用。
方法
我们使用了老年 β-淀粉样变性的 APPPS1 转基因模型，并在两种治疗模式（发病前和发病后）中用 DMF 口服治疗雌性小鼠。我们量化了学习和记忆参数、β-淀粉样变性和神经炎症，以确定 DMF 作为 AD 治疗剂的潜力。
结果
DMF 治疗对水迷宫性能、β-淀粉样蛋白积累、斑块形成、小胶质细胞活化和免疫细胞向大脑的募集没有影响。与载体治疗的动物相比，口服 DMF 治疗不能阻止或延缓小鼠的疾病进展。
讨论
我们的结果不赞成使用 DMF 作为 AD 的治疗方法。虽然我们的结果与之前在其他模型中的发现形成鲜明对比，但他们强调了动物模型选择的重要性，并建议进一步研究以阐明导致相互矛盾的结果的机制。
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