Purpose

Alzheimer’s disease (AD) is a progressive neurodegenerative pathological condition that resulted from the deterioration of cholinergic neurons over time. The pathological hallmark features of AD include extracellular β-amyloids plaques, hyperphosphorylated τ protein (tau), which is the main component of neurofibrillary tangles (NFT) and neuroinflammation. This article aims to provide a comprehensive review of PET tracers for Alzheimer’s disease, focusing on developments for targets (β-amyloids, hyperphosphorylated τ protein (tau), neuroinflammation and other related targets) available for clinical PET imaging.

Methods/design

Studies involving the existing PET tracers used in the imaging of Aβ, tau, and neuroinflammation with essential features and limitations are discussed. Experimental studies with the design perspective of PET tracers, for biomarkers like Aβ, tau protein, and neuroinflammation, which are exploited clinically through PET Imaging have been described in detail. Comparative data have been generated based on the strength and weakness of PET radioligands for preclinical and clinical studies based on their binding affinity, selectivity and imaging. PET tracers for other targets like cannabinoid receptor type 2 (CB2), P2X7 receptor, cyclooxygenase-2, macrophage colony-stimulating factor 1 receptor (CSF1R), and monoamine oxidase (MAO) have also been included.

Result

We have summarized the ideal properties in terms of tracer's design for each target and based on their target selectivity and affinity, considering its potential strength and limitations. Where multiple tracers were present for a target, we provide a comparison of their properties. A critical assessment of both the preclinical and clinical PET tracers is carried out where sufficient data are available. This can help in designing better and highly selective PET tracers.

Conclusion

Our comprehensive review will provide comparison and help in the design perspective of the futuristic PET tracers for Alzheimer's disease by improving their affinity towards biomarkers with higher selectivity Aβ/tau for delineation of AD at an early stage.

Graphic abstract

中文翻译：

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基于β-淀粉样蛋白，tau和神经炎症的PET配体设计观点的综合综述，用于阿尔茨海默氏病的诊断干预

目的

阿尔茨海默氏病（AD）是一种由进行性胆碱能神经元退化引起的神经退行性病理疾病。AD的病理特征包括细胞外β淀粉样蛋白斑块，磷酸化的τ蛋白（tau），它是神经原纤维缠结（NFT）和神经炎症的主要成分。本文旨在提供针对阿尔茨海默氏病的PET示踪剂的全面综述，重点关注可用于临床PET显像的靶标（β-淀粉样蛋白，高磷酸化τ蛋白（tau），神经炎症和其他相关靶标）的开发。

方法/设计

讨论了涉及用于Aβ，tau和神经炎症成像的现有PET示踪剂的研究，这些示踪剂具有基本特征和局限性。已经详细描述了从PET示踪剂的设计角度进行的针对Aβ，tau蛋白和神经炎症等生物标记物的实验研究，这些生物标记物是通过PET成像在临床上开发的。基于PET放射性配体的强项和弱项，已根据其结合亲和力，选择性和成像进行了临床前和临床研究，得出了比较数据。还包括针对其他靶标的PET示踪剂，例如2型大麻受体（CB2），P2X7受体，环加氧酶2，巨噬细胞集落刺激因子1受体（CSF1R）和单胺氧化酶（MAO）。

结果

我们根据示踪剂的设计，针对每个目标并根据目标的选择性和亲和力总结了理想的特性，并考虑了其潜在的强度和局限性。当一个目标存在多个示踪剂时，我们提供它们的特性的比较。在有足够数据的情况下，对临床前和临床PET示踪剂都进行了严格的评估。这可以帮助设计更好和选择性更高的PET示踪剂。

结论

我们的全面综述将通过改善早期对动物标记物的亲和力，通过提高它们对具有较高选择性Aβ/ tau的生物标记物的亲和力，从而在AD勾画中提供比较和帮助，以用于阿尔茨海默氏病的未来性PET示踪剂。

图形摘要