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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
Antonioni A, Raho EM, Di Lorenzo F, Manzoli L, Flacco ME, Koch G.. Journal of neurology, 2025-03-06
Topic: Amyloid, tau and blood-test diagnosis
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.
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APA 7th
Antonioni, A., Raho, E. M., Di Lorenzo, F., Manzoli, L., Flacco, M. E., & Koch, G. (2025). Blood phosphorylated Tau217 distinguishes amyloid-positive from amyloid-negative subjects in the Alzheimer's disease continuum. A systematic review and meta-analysis. Journal of neurology. https://doi.org/10.1007/s00415-025-12996-3
Vancouver
Antonioni A, Raho EM, Di Lorenzo F, Manzoli L, Flacco ME, Koch G. Blood phosphorylated Tau217 distinguishes amyloid-positive from amyloid-negative subjects in the Alzheimer's disease continuum. A systematic review and meta-analysis. Journal of neurology. 2025. doi:10.1007/s00415-025-12996-3. PMID: 40047958.
BibTeX
@article{antonioni2025-40047958,
author = {Antonioni, A. and Raho, E. M. and Di Lorenzo, F. and Manzoli, L. and Flacco, M. E. and Koch, G.},
title = {{Blood phosphorylated Tau217 distinguishes amyloid-positive from amyloid-negative subjects in the Alzheimer's disease continuum. A systematic review and meta-analysis}},
journal = {Journal of neurology},
year = {2025},
doi = {10.1007/s00415-025-12996-3},
pmid = {40047958},
url = {https://doi.org/10.1007/s00415-025-12996-3}
}
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Key findings
- 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.
- 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.
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Study details
- Study designsystematic review
- Evidence strengthHigh
How this study scored 72/100
Published in a peer-reviewed journal, and it is a systematic review of all the studies on the question. Scored zero for sample size, effect reported and studied in people because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 42 of the 58 points we could judge it on, which is 72 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neurology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 12 / 12 | A systematic review of all the studies on the question |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | A review of other studies — randomization is not credited here |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40047958) |
| Free to read | 2 / 2 | Free to read |
| Points | 42 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 42 of the 58 points we could judge it on is 72 out of 100. |
| Total | 72 / 100 | — |
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