Generation and Characterization of a Human-Derived and Induced Pluripotent Stem Cell (iPSC) Line from an Alzheimer's Disease Patient with Neuropsychiatric Symptoms.
Generation and Characterization of a Human-Derived and Induced Pluripotent Stem Cell (iPSC) Line from an Alzheimer's Disease Patient with Neuropsychiatric Symptoms.
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DOI：
10.3390/biomedicines11123313
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发表时间：
2023-12-15
期刊：
影响因子：
4.7
通讯作者：
Mahairaki, Vasiliki
中科院分区：
文献类型：
--
作者：
Sagar, Ram;Zivko, Cristina;Xydia, Ariadni;Weisman, David C.;Lyketsos, Constantine G.;Mahairaki, Vasiliki
躁动是影响阿尔茨海默氏症和痴呆症患者的神经精神症状（NPSs）的最显著特征之一，对患者和护理人员具有严重后果。目前的共识是，激动的结果，部分原因是由于皮质回路的上行单胺调节剂的破坏，特别是多巴胺能活性的丧失。据信，治疗这些疾病的第一线是选择性5-羟色胺再摄取抑制剂（SSRI），但这些药物仅对约40%的患者有效。个人特异性生物标志物，例如，基于体外iPSC衍生的5-羟色胺活性模型的生物标志物，可以预测谁对SSRI有反应，这是一个主要的临床优先事项。在这里，我们报告了从一名74岁的AD患者（纯合子APOE ε4/ε4携带者）中产生的人类诱导多能干细胞（iPSC），该患者患有躁动症。使用多能性基因的瞬时表达从外周血单核细胞（PBMC）重编程他的iPSC。这些细胞显示出典型的iPSC特征，即核型正常，并具有分化成三个胚层的能力。新的患者来源的iPSC系提供了一个独特的资源，以调查与AD的神经精神症状进展相关的潜在机制。
Agitation is one of the most eminent characteristics of neuropsychiatric symptoms (NPS) affecting people living with Alzheimer’s and Dementia and has serious consequences for patients and caregivers. The current consensus is that agitation results, in part, from the disruption of ascending monoamine regulators of cortical circuits, especially the loss of serotonergic activity. It is believed that the first line of treatment for these conditions is selective serotonin reuptake inhibitors (SSRIs), but these are effective in only about 40% of patients. Person-specific biomarkers, for example, ones based on in vitro iPSC-derived models of serotonin activity, which predict who with Agitation responds to an SSRI, are a major clinical priority. Here, we report the generation of human-induced pluripotent stem cells (iPSCs) from a 74-year-old AD patient, the homozygous APOE ε4/ε4 carrier, who developed Agitation. His iPSCs were reprogrammed from peripheral blood mononuclear cells (PBMCs) using the transient expression of pluripotency genes. These display typical iPSC characteristics that are karyotypically normal and attain the capacity to differentiate into three germ layers. The newly patient-derived iPSC line offers a unique resource to investigate the underlying mechanisms associated with neuropsychiatric symptom progression in AD.
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