PDF(Pubmed)
Abstract：
Alzheimer\'s disease (AD) is a prevalent neurodegenerative disorder without a cure. Innovative disease models, such as induced neurons (iNs), could enhance our understanding of AD mechanisms and accelerate treatment development. However, a review of AD human iN studies is necessary to consolidate knowledge.
The objective of this review is to examine the current body of literature on AD human iN cells and provide an overview of the findings to date.
We searched two databases for relevant studies published between 2010 and 2023, identifying nine studies meeting our criteria.
Reviewed studies indicate the feasibility of generating iNs directly from AD patients\' fibroblasts using chemical induction or viral vectors. These cells express mature neuronal markers, including MAP-2, NeuN, synapsin, and tau. However, most studies were limited in sample size and primarily focused on autosomal dominant familial AD (FAD) rather than the more common sporadic forms of AD. Several studies indicated that iNs derived from FAD fibroblasts exhibited abnormal amyloid-β metabolism, a characteristic feature of AD in humans. Additionally, elevated levels of hyperphosphorylated tau, another hallmark of AD, were reported in some studies.
Although only a limited number of small-scale studies are currently available, AD patient-derived iNs hold promise as a valuable model for investigating AD pathogenesis. Future research should aim to conduct larger studies, particularly focusing on sporadic AD cases, to enhance the clinical relevance of the findings for the broader AD patient population. Moreover, these cells can be utilized in screening potential novel treatments for AD.
The objective of this review is to examine the current body of literature on AD human iN cells and provide an overview of the findings to date.
We searched two databases for relevant studies published between 2010 and 2023, identifying nine studies meeting our criteria.
Reviewed studies indicate the feasibility of generating iNs directly from AD patients\' fibroblasts using chemical induction or viral vectors. These cells express mature neuronal markers, including MAP-2, NeuN, synapsin, and tau. However, most studies were limited in sample size and primarily focused on autosomal dominant familial AD (FAD) rather than the more common sporadic forms of AD. Several studies indicated that iNs derived from FAD fibroblasts exhibited abnormal amyloid-β metabolism, a characteristic feature of AD in humans. Additionally, elevated levels of hyperphosphorylated tau, another hallmark of AD, were reported in some studies.
Although only a limited number of small-scale studies are currently available, AD patient-derived iNs hold promise as a valuable model for investigating AD pathogenesis. Future research should aim to conduct larger studies, particularly focusing on sporadic AD cases, to enhance the clinical relevance of the findings for the broader AD patient population. Moreover, these cells can be utilized in screening potential novel treatments for AD.
摘要：
背景：阿尔茨海默病（AD）是一种普遍的神经退行性疾病，无法治愈。创新的疾病模型，如诱导神经元(iNs)，可以增强我们对AD机制的理解，加速治疗发展。然而,对AD人类iN研究的回顾对于巩固知识是必要的。
目的：这篇综述的目的是研究目前关于AD人iN细胞的大量文献，并对迄今为止的发现进行概述。
方法：我们在两个数据库中搜索了2010年至2023年间发表的相关研究，确定了9项符合我们标准的研究。
结果：回顾的研究表明，使用化学诱导或病毒载体直接从AD患者成纤维细胞产生iN的可行性。这些细胞表达成熟的神经元标记，包括MAP-2NeuN,突触素，还有tau.然而,大多数研究的样本量有限,主要集中于常染色体显性遗传家族性AD(FAD),而不是更常见的偶发性AD.一些研究表明，来自FAD成纤维细胞的iN表现出异常的淀粉样β代谢，人类AD的特征。此外,高磷酸化tau水平升高，AD的另一个标志,在一些研究中报道。
结论：尽管目前只有有限数量的小规模研究，AD患者来源的iN有望成为研究AD发病机理的有价值的模型。未来的研究应该旨在进行更大的研究，特别是集中在零星的AD病例，以增强更广泛的AD患者群体的临床相关性。此外，这些细胞可用于筛选潜在的新型AD治疗方法。
目的：这篇综述的目的是研究目前关于AD人iN细胞的大量文献，并对迄今为止的发现进行概述。
方法：我们在两个数据库中搜索了2010年至2023年间发表的相关研究，确定了9项符合我们标准的研究。
结果：回顾的研究表明，使用化学诱导或病毒载体直接从AD患者成纤维细胞产生iN的可行性。这些细胞表达成熟的神经元标记，包括MAP-2NeuN,突触素，还有tau.然而,大多数研究的样本量有限,主要集中于常染色体显性遗传家族性AD(FAD),而不是更常见的偶发性AD.一些研究表明，来自FAD成纤维细胞的iN表现出异常的淀粉样β代谢，人类AD的特征。此外,高磷酸化tau水平升高，AD的另一个标志,在一些研究中报道。
结论：尽管目前只有有限数量的小规模研究，AD患者来源的iN有望成为研究AD发病机理的有价值的模型。未来的研究应该旨在进行更大的研究，特别是集中在零星的AD病例，以增强更广泛的AD患者群体的临床相关性。此外，这些细胞可用于筛选潜在的新型AD治疗方法。
