具有与突触小泡糖蛋白2A(SV2A)结合的放射性示踪剂的正电子发射断层扫描(PET)能够定量活人脑中的突触密度。评估突触密度损失的区域分布和严重程度将有助于我们了解神经变性萎缩之前的病理过程。在这次系统审查中,我们提供了体内SV2APET成像研究的讨论,用于定量评估各种痴呆条件下的突触密度:遗忘轻度认知障碍和阿尔茨海默病,额颞叶痴呆,进行性核上性麻痹和皮质基底变性,帕金森病和路易体痴呆,亨廷顿病,和脊髓小脑共济失调.我们讨论了关于群体差异和临床认知相关性的主要发现,探讨SV2APET与其他病理标志物的关系。此外,我们涉及健康衰老中的突触密度和放射性示踪剂验证研究的结果。在2018年至2023年之间在PubMed和Embase上进行了研究;最后一次搜索是在2023年7月3日。共纳入36项研究,包括正常老化的5,21项临床研究,和10个验证研究。提取的研究特征是参与者的细节,方法论方面,和重要的发现。总之,关于体内SV2APET的少量但不断增长的文献揭示了与认知功能相关的各种神经退行性疾病中突触密度损失的不同空间模式,支持SV2APET成像在鉴别诊断中的潜在作用。SV2APET成像显示出巨大的能力,可以为神经退行性疾病的病因提供新的见解,并且有望作为突触密度降低的生物标志物。提出了未来突触密度研究的新方向,包括(a)在临床前痴呆的较大患者队列中进行纵向成像,(b)突触密度损失到其他病理过程的多模态映射,和(c)在临床试验中监测治疗反应和评估药物疗效。
Positron emission tomography (PET) with radiotracers that bind to synaptic vesicle glycoprotein 2 A (
SV2A) enables quantification of synaptic density in the living human brain. Assessing the regional distribution and severity of synaptic density loss will contribute to our understanding of the pathological processes that precede atrophy in neurodegeneration. In this systematic review, we provide a discussion of in vivo
SV2A PET imaging research for quantitative assessment of synaptic density in various dementia conditions: amnestic Mild Cognitive Impairment and Alzheimer\'s disease, Frontotemporal dementia, Progressive supranuclear palsy and Corticobasal degeneration, Parkinson\'s disease and Dementia with Lewy bodies, Huntington\'s disease, and Spinocerebellar Ataxia. We discuss the main findings concerning group differences and clinical-cognitive correlations, and explore relations between
SV2A PET and other markers of pathology. Additionally, we touch upon synaptic density in healthy ageing and outcomes of radiotracer validation studies. Studies were identified on PubMed and Embase between 2018 and 2023; last searched on the 3rd of July 2023. A total of 36 studies were included, comprising 5 on normal ageing, 21 clinical studies, and 10 validation studies. Extracted study characteristics were participant details, methodological aspects, and critical findings. In summary, the small but growing literature on in vivo
SV2A PET has revealed different spatial patterns of synaptic density loss among various neurodegenerative disorders that correlate with cognitive functioning, supporting the potential role of
SV2A PET imaging for differential diagnosis. SV2A PET imaging shows tremendous capability to provide novel insights into the aetiology of neurodegenerative disorders and great promise as a biomarker for synaptic density reduction. Novel directions for future synaptic density research are proposed, including (a) longitudinal imaging in larger patient cohorts of preclinical dementias, (b) multi-modal mapping of synaptic density loss onto other pathological processes, and (c) monitoring therapeutic responses and assessing drug efficacy in clinical trials.