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Background <p>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.</p> Methods <p>We performed a systematic&#xa0;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.</p> Results <p>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.</p> Conclusions <p>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.</p> Clinical trial registration <p>Prospero CRD42024565187</p>

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Blood phosphorylated Tau217 distinguishes amyloid-positive from amyloid-negative subjects in the Alzheimer's disease continuum. A systematic review and meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月6日

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  • Annibale Antonioni,
  • Emanuela Maria Raho,
  • Francesco Di Lorenzo,
  • Lamberto Manzoli,
  • Maria Elena Flacco,
  • Giacomo Koch

摘要

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Clinical trial registration

Prospero CRD42024565187