The translational power of Alzheimer's-based organoid models in personalized medicine: an integrated biological and digital approach embodying patient clinical history.

IF 4.2 3区 医学 Q2 NEUROSCIENCES
Frontiers in Cellular Neuroscience Pub Date : 2025-05-15 eCollection Date: 2025-01-01 DOI:10.3389/fncel.2025.1553642
Cristina Dolciotti, Marco Righi, Eleonora Grecu, Marcello Trucas, Cristina Maxia, Daniela Murtas, Andrea Diana
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引用次数: 0

Abstract

Alzheimer's disease (AD) is a complex neurodegenerative condition characterized by a multifaceted interplay of genetic, environmental, and pathological factors. Traditional diagnostic and research methods, including neuropsychological assessments, imaging, and cerebrospinal fluid (CSF) biomarkers, have advanced our understanding but remain limited by late-stage detection and challenges in modeling disease progression. The emergence of three-dimensional (3D) brain organoids (BOs) offers a transformative platform for bridging these gaps. BOs derived from patient-specific induced pluripotent stem cells (iPSCs) mimic the structural and functional complexities of the human brain. This advancement offers an alternative or complementary approach for studying AD pathology, including β-amyloid and tau protein aggregation, neuroinflammation, and aging processes. By integrating biological complexity with cutting-edge technological tools such as organ-on-a-chip systems, microelectrode arrays, and artificial intelligence-driven digital twins (DTs), it is hoped that BOs will facilitate real-time modeling of AD progression and response to interventions. These models capture central nervous system biomarkers and establish correlations with peripheral markers, fostering a holistic understanding of disease mechanisms. Furthermore, BOs provide a scalable and ethically sound alternative to animal models, advancing drug discovery and personalized therapeutic strategies. The convergence of BOs and DTs potentially represents a significant shift in AD research, enhancing predictive and preventive capacities through precise in vitro simulations of individual disease trajectories. This approach underscores the potential for personalized medicine, reducing the reliance on invasive diagnostics while promoting early intervention. As research progresses, integrating sporadic and familial AD models within this framework promises to refine our understanding of disease heterogeneity and drive innovations in treatment and care.

基于阿尔茨海默病的类器官模型在个性化医疗中的转化能力:一种体现患者临床病史的综合生物学和数字方法。
阿尔茨海默病(AD)是一种复杂的神经退行性疾病,其特征是遗传、环境和病理因素的多方面相互作用。传统的诊断和研究方法,包括神经心理学评估、成像和脑脊液(CSF)生物标志物,已经提高了我们的理解,但仍然受到后期检测和疾病进展建模的挑战的限制。三维脑类器官(BOs)的出现为弥合这些差距提供了一个变革性的平台。来源于患者特异性诱导多能干细胞(iPSCs)的BOs模拟了人类大脑的结构和功能复杂性。这一进展为研究阿尔茨海默病的病理,包括β-淀粉样蛋白和tau蛋白聚集,神经炎症和衰老过程提供了替代或补充的方法。通过将生物复杂性与尖端技术工具(如器官芯片系统、微电极阵列和人工智能驱动的数字双胞胎(dt))相结合,希望BOs能够促进AD进展和干预反应的实时建模。这些模型捕获中枢神经系统生物标志物,并建立与外周标志物的相关性,促进对疾病机制的整体理解。此外,动物模型提供了一种可扩展且合乎伦理的替代方法,促进了药物发现和个性化治疗策略。BOs和DTs的融合可能代表着AD研究的重大转变,通过对个体疾病轨迹的精确体外模拟,增强了预测和预防能力。这种方法强调了个性化医疗的潜力,减少了对侵入性诊断的依赖,同时促进了早期干预。随着研究的进展,在这个框架内整合散发性和家族性AD模型有望完善我们对疾病异质性的理解,并推动治疗和护理方面的创新。
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来源期刊
CiteScore
7.90
自引率
3.80%
发文量
627
审稿时长
6-12 weeks
期刊介绍: Frontiers in Cellular Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the cellular mechanisms underlying cell function in the nervous system across all species. Specialty Chief Editors Egidio D‘Angelo at the University of Pavia and Christian Hansel at the University of Chicago are supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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