This manuscript presents a thorough review of synaptic vesicle glycoprotein 2A (SV2A) as a biomarker for synaptic integrity using Positron Emission Tomography (PET) in neurodegenerative diseases. Synaptic pathology, characterized by synaptic loss, has been linked to various brain diseases. Therefore, there is a need for a minimally invasive approach to measuring synaptic density in living human patients. Several radiotracers targeting synaptic vesicle protein 2A (SV2A) have been created and effectively adapted for use in human subjects through PET scans. SV2A is an integral glycoprotein found in the membranes of synaptic vesicles in all synaptic terminals and is widely distributed throughout the brain. The review delves into the development of SV2A-specific PET radiotracers, highlighting their advancements and limitations in neurodegenerative diseases. Among these tracers, 11C-UCB-J is the most used so far. We summarize and discuss an increasing body of research that compares measurements of synaptic density using SV2A PET with other established indicators of neurodegenerative diseases, including cognitive performance and radiological findings, thus providing a comprehensive analysis of SV2A’s effectiveness and reliability as a diagnostic tool in contrast to traditional markers. Although the literature overall suggests the promise of SV2A as a diagnostic and therapeutic monitoring tool, uncertainties persist regarding the superiority of SV2A as a biomarker compared to other available markers. The review also underscores the paucity of studies characterizing SV2A distribution and loss in human brain tissue from patients with neurodegenerative diseases, emphasizing the need to generate quantitative neuropathological maps of SV2A density in cases with neurodegenerative diseases to fully harness the potential of SV2A PET imaging in clinical settings. We conclude by outlining future research directions, stressing the importance of integrating SV2A PET imaging with other biomarkers and clinical assessments and the need for longitudinal studies to track SV2A changes throughout neurodegenerative disease progression, which could lead to breakthroughs in early diagnosis and the evaluation of new treatments.

中文翻译：

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SV2A PET 成像在人类神经退行性疾病中的应用

本手稿对突触小泡糖蛋白 2A (SV2A) 作为神经退行性疾病中突触完整性生物标志物使用正电子发射断层扫描 (PET) 进行了全面综述。以突触损失为特征的突触病理学与多种脑部疾病有关。因此，需要一种微创方法来测量活体人类患者的突触密度。几种针对突触小泡蛋白 2A (SV2A) 的放射性示踪剂已经被创造出来，并通过 PET 扫描有效地用于人类受试者。 SV2A 是一种整合糖蛋白，存在于所有突触末梢的突触小泡膜中，广泛分布于整个大脑。该综述深入研究了 SV2A 特异性 PET 放射性示踪剂的开发，强调了它们在神经退行性疾病方面的进展和局限性。在这些示踪剂中，11C-UCB-J是迄今为止使用最多的。我们总结并讨论了越来越多的研究，这些研究将使用 SV2A PET 测量的突触密度与其他既定的神经退行性疾病指标（包括认知表现和放射学结果）进行比较，从而对 SV2A 作为诊断工具的有效性和可靠性进行了全面分析。传统标记。尽管文献总体表明 SV2A 作为诊断和治疗监测工具的前景，但与其他可用标记物相比，SV2A 作为生物标记物的优越性仍然存在不确定性。该综述还强调了缺乏神经退行性疾病患者脑组织中 SV2A 分布和损失的研究，强调需要在神经退行性疾病病例中生成 SV2A 密度的定量神经病理图，以充分利用 SV2A PET 成像在临床中的潜力设置。最后，我们概述了未来的研究方向，强调将 SV2A PET 成像与其他生物标志物和临床评估相结合的重要性，以及进行纵向研究来跟踪整个神经退行性疾病进展过程中 SV2A 变化的必要性，这可能会在早期诊断和评估新药物方面带来突破。治疗。