Abstract：
BACKGROUND: The degeneration of cortical layers is associated with cognitive decline in Alzheimer\'s disease (AD). Current therapies for AD are not disease-modifying, and, despite substantial efforts, research and development for AD has faced formidable challenges. In addition, cellular senescence has emerged as a significant contributor to therapy resistance.
METHODS: Human iPSC-derived cortical neurons were cultured on microelectrode arrays to measure long-term potentiation (LTP) noninvasively. Neurons were treated with pathogenic amyloid-β (Aβ) to analyze senescence and response to therapeutic molecules.
RESULTS: Microphysiological recordings revealed Aβ dampened cortical LTP activity and accelerated neuronal senescence. Aging neurons secreted inflammatory factors previously detected in brain, plasma, and cerebral spinal fluid of AD patients, in which drugs modulated senescence-related factors.
CONCLUSIONS: This platform measures and records neuronal LTP activity in response to Aβ and therapeutic molecules in real-time. Efficacy data from similar platforms have been accepted by the FDA for neurodegenerative diseases, expediting regulatory submissions.
CONCLUSIONS: This work developed a progerontic model of amyloid-β (Aβ)-driven cortical degeneration. This work measured neuronal LTP and correlated function with aging biomarkers. Aβ is a driver of neuronal senescence and cortical degeneration. Molecules rescued neuronal function but did not halt Aβ-driven senescence. Therapeutic molecules modulated secretion of inflammatory factors by aging neurons.
METHODS: Human iPSC-derived cortical neurons were cultured on microelectrode arrays to measure long-term potentiation (LTP) noninvasively. Neurons were treated with pathogenic amyloid-β (Aβ) to analyze senescence and response to therapeutic molecules.
RESULTS: Microphysiological recordings revealed Aβ dampened cortical LTP activity and accelerated neuronal senescence. Aging neurons secreted inflammatory factors previously detected in brain, plasma, and cerebral spinal fluid of AD patients, in which drugs modulated senescence-related factors.
CONCLUSIONS: This platform measures and records neuronal LTP activity in response to Aβ and therapeutic molecules in real-time. Efficacy data from similar platforms have been accepted by the FDA for neurodegenerative diseases, expediting regulatory submissions.
CONCLUSIONS: This work developed a progerontic model of amyloid-β (Aβ)-driven cortical degeneration. This work measured neuronal LTP and correlated function with aging biomarkers. Aβ is a driver of neuronal senescence and cortical degeneration. Molecules rescued neuronal function but did not halt Aβ-driven senescence. Therapeutic molecules modulated secretion of inflammatory factors by aging neurons.
摘要：
背景：皮质层的退化与阿尔茨海默病（AD）的认知能力下降有关。目前的AD治疗方法不是疾病的改变，and,尽管付出了巨大的努力，AD的研究和开发面临着巨大的挑战。此外,细胞衰老已成为治疗抗性的重要因素。
方法：在微电极阵列上培养人iPSC来源的皮质神经元，以无创地测量长期增强（LTP）。用致病性淀粉样蛋白-β(Aβ)处理神经元以分析衰老和对治疗分子的反应。
结果：微生理记录显示Aβ抑制皮质LTP活性并加速神经元衰老。先前在脑中检测到的衰老神经元分泌炎症因子，等离子体,和AD患者的脑脊液，其中药物调节衰老相关因子。
结论：该平台实时测量并记录响应Aβ和治疗分子的神经元LTP活性。来自类似平台的功效数据已被FDA接受，用于治疗神经退行性疾病。加快监管提交。
结论：这项工作开发了淀粉样蛋白β（Aβ）驱动的皮质变性的早衰模型。这项工作测量了神经元LTP，并与衰老生物标志物相关。Aβ是神经元衰老和皮质变性的驱动因素。分子挽救了神经元功能，但并未阻止Aβ驱动的衰老。治疗分子通过衰老神经元调节炎症因子的分泌。
方法：在微电极阵列上培养人iPSC来源的皮质神经元，以无创地测量长期增强（LTP）。用致病性淀粉样蛋白-β(Aβ)处理神经元以分析衰老和对治疗分子的反应。
结果：微生理记录显示Aβ抑制皮质LTP活性并加速神经元衰老。先前在脑中检测到的衰老神经元分泌炎症因子，等离子体,和AD患者的脑脊液，其中药物调节衰老相关因子。
结论：该平台实时测量并记录响应Aβ和治疗分子的神经元LTP活性。来自类似平台的功效数据已被FDA接受，用于治疗神经退行性疾病。加快监管提交。
结论：这项工作开发了淀粉样蛋白β（Aβ）驱动的皮质变性的早衰模型。这项工作测量了神经元LTP，并与衰老生物标志物相关。Aβ是神经元衰老和皮质变性的驱动因素。分子挽救了神经元功能，但并未阻止Aβ驱动的衰老。治疗分子通过衰老神经元调节炎症因子的分泌。
