Antonioni Annibale, Raho Emanuela Maria, Di Lorenzo Francesco, Manzoli Lamberto, Flacco Maria Elena, Koch Giacomo
Doctoral Program in Translational Neurosciences and Neurotechnologies, Department of Neuroscience and Rehabilitation, University of Ferrara, Via Ludovico Ariosto, 35, 44121, Ferrara, Italy.
Department of Neuroscience and Rehabilitation, University of Ferrara, 44121, Ferrara, Italy.
J Neurol. 2025 Mar 6;272(3):252. doi: 10.1007/s00415-025-12996-3.
Alzheimer's disease (AD) is the leading cause of dementia worldwide, and cost-effective tools to detect amyloid pathology are urgently needed. Blood-based Tau phosphorylated at threonine 217 (pTau217) seems promising, but its reliability as a proxy for cerebrospinal fluid (CSF) status and ability to identify patients within the AD spectrum remain unclear.
We performed a systematic review and meta-analysis on the potential of blood pTau217 to differentiate amyloid-positive (A+) and amyloid-negative (A-) subjects. We included original studies reporting quantitative data on pTau217 concentrations in both blood and CSF in the AD continuum. The single-group meta-analysis computed the pooled pTau217 levels in blood and in CSF, separately in the A+ and A- groups, while the head-to-head meta-analysis compared the mean pTau217 concentrations in the A+ versus A- subjects, both in blood and CSF, stratifying by assessment method in both cases.
Ten studies (819 A+; 1055 A-) were included. The mean pTau217 levels resulted higher in CSF than in blood and, crucially, in A+ individuals than in A- ones, regardless of the laboratory method employed. Most importantly, all laboratory techniques reliably distinguished A+ from A- subjects, whether applied to CSF or blood samples.
These results confirm that blood-based pTau217 is a reliable marker of amyloid pathology with significant implications for clinical practice in the AD continuum. Indeed, pTau217 might be a non-invasive, scalable biomarker for early AD detection, reducing the reliance on more invasive, expansive, and less accessible methods.
Prospero CRD42024565187.
阿尔茨海默病（AD）是全球痴呆的主要病因，迫切需要具有成本效益的工具来检测淀粉样蛋白病变。血液中苏氨酸217位点磷酸化的 Tau 蛋白（pTau217）似乎很有前景，但其作为脑脊液（CSF）状态替代指标的可靠性以及在AD谱系中识别患者的能力仍不明确。
我们对血液中pTau217区分淀粉样蛋白阳性（A+）和淀粉样蛋白阴性（A-）受试者的潜力进行了系统评价和荟萃分析。我们纳入了报告AD连续体中血液和CSF中pTau217浓度定量数据的原始研究。单组荟萃分析分别计算了A+组和A-组血液和CSF中pTau217的合并水平，而头对头荟萃分析比较了A+与A-受试者血液和CSF中pTau217的平均浓度，并在两种情况下按评估方法进行分层。
纳入了10项研究（819例A+；1055例A-）。无论采用何种实验室方法，CSF中pTau217的平均水平均高于血液，至关重要的是，A+个体中的水平高于A-个体。最重要的是，所有实验室技术都能可靠地区分A+和A-受试者，无论应用于CSF还是血液样本。
这些结果证实，血液中的pTau217是淀粉样蛋白病变的可靠标志物，对AD连续体的临床实践具有重要意义。事实上，pTau217可能是一种用于早期AD检测的非侵入性、可扩展的生物标志物，减少了对更具侵入性、费用更高且难以获取的方法的依赖。
Prospero CRD42024565187。
