Induced pluripotent stem-cell-based models enable investigation of pathomechanisms in disease-relevant human brain cell types and therefore offer great potential for mechanistic and translational studies on neurodegenerative disorders, such as Alzheimer's disease (AD). While current AD models allow analysis of early disease phenotypes including Aβ accumulation and Tau hyperphosphorylation, they still fail to fully recapitulate later hallmarks such as protein aggregation and neurodegeneration. This impedes the identification of pathomechanisms and novel therapeutic targets. We discuss strategies to overcome these drawbacks and optimize physiological properties and translational potential of iPSC-based models by improving culture formats, increasing cellular diversity, applying genome editing, and implementing maturation and ageing paradigms.

中文翻译：

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菜肴中的神经变性：促进基于人类干细胞的阿尔茨海默氏病模型。

诱导的基于多能干细胞的模型能够研究与疾病相关的人类脑细胞类型中的致病机理，因此为神经退行性疾病（例如阿尔茨海默氏病（AD））的机理和转化研究提供了巨大潜力。尽管当前的AD模型可以分析包括Aβ积累和Tau过度磷酸化在内的早期疾病表型，但它们仍无法完全概括蛋白质标记和神经变性等后期特征。这阻碍了病理机制和新型治疗靶标的鉴定。我们讨论了克服这些缺点并通过改善培养形式，增加细胞多样性，应用基因组编辑以及实施成熟和衰老范式来优化基于iPSC的模型的生理特性和翻译潜力的策略。