Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Department of Neurodegeneration Diagnostics, Medical University of Bialystok, Bialystok, Poland.
Neurol Neurochir Pol. 2024;58(4):363-379. doi: 10.5603/pjnns.100675. Epub 2024 Aug 2.
The number of patients with Alzheimer's Disease (AD) has increased rapidly in recent decades. AD is a complex progressive neurodegenerative disease affecting c.14 million patients in Europe and the United States. The hallmarks of this disease are neurotic plaques composed of the amyloid-β (Aβ) peptide and neurofibrillary tangles formed of hyperphosphorylated tau protein (pTau). To date, four CSF biomarkers: amyloid beta 42 (Aβ42), Aβ42/40 ratio, Tau protein, and Tau phosphorylated at threonine 181 (pTau181) have been validated as core neurochemical AD biomarkers. Imaging biomarkers are valuable for AD diagnosis, although they suffer from limitations in their cost and accessibility, while CSF biomarkers require lumbar puncture. Thus, there is an urgent need for alternative, less invasive and more cost-effective biomarkers capable of diagnosing and monitoring AD progression in a clinical context, as well as expediting the development of new therapeutic strategies. This review assesses the potential clinical significance of plasma candidate biomarkers in AD diagnosis. We conclude that these proteins might hold great promise in identifying the pathological features of AD. However, the future implementation process, and validation of the assays' accuracy using predefined cut-offs across more diverse patient populations, are crucial in establishing their utility in daily practice.
在过去几十年中，阿尔茨海默病（AD）患者的数量迅速增加。AD 是一种复杂的进行性神经退行性疾病，影响欧洲和美国约 1400 万患者。这种疾病的特征是由淀粉样β（Aβ）肽组成的神经斑块和由过度磷酸化的 tau 蛋白（pTau）形成的神经原纤维缠结。迄今为止，四种 CSF 生物标志物：β淀粉样蛋白 42（Aβ42）、Aβ42/40 比值、Tau 蛋白和 Tau 在苏氨酸 181 处磷酸化（pTau181）已被验证为核心神经化学 AD 生物标志物。成像生物标志物对 AD 的诊断具有重要价值，但它们在成本和可及性方面存在局限性，而 CSF 生物标志物则需要腰椎穿刺。因此，迫切需要替代的、微创的、更具成本效益的生物标志物，能够在临床环境中诊断和监测 AD 的进展，并加速新的治疗策略的开发。本综述评估了血浆候选生物标志物在 AD 诊断中的潜在临床意义。我们得出结论，这些蛋白质可能在识别 AD 的病理特征方面具有很大的潜力。然而，未来的实施过程以及使用预定义的截止值在更多样化的患者群体中验证这些检测的准确性，对于确定它们在日常实践中的实用性至关重要。
