Evidence map›Paper›PMID 42101517›Full record

ArticleJournal of neurology2026

Streamlining Alzheimer's disease diagnosis: real-world validation of two-cut-off diagnostic models based on plasma p-tau/Aβ42 ratios.

Martina Poli, Chiara Giuseppina Bonomi, Martina Gaia Di Donna, Ilaria Barberis, Emanuele Luca Ginevra, Marzia Nuccetelli, Sergio Bernardini, Diego Centonze, Alessandro Martorana, Caterina Motta

Abstract readValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Martina Poli *Memory Clinic and Neurodegenerative Dementia Research Unit, Policlinico Tor Vergata, University of Rome "Tor Vergata", viale Oxford 81, 00133, Rome, Italy.
Chiara Giuseppina Bonomi *Memory Clinic and Neurodegenerative Dementia Research Unit, Policlinico Tor Vergata, University of Rome "Tor Vergata", viale Oxford 81, 00133, Rome, Italy.
Martina Gaia Di DonnaMemory Clinic and Neurodegenerative Dementia Research Unit, Policlinico Tor Vergata, University of Rome "Tor Vergata", viale Oxford 81, 00133, Rome, Italy.
Ilaria BarberisMemory Clinic and Neurodegenerative Dementia Research Unit, Policlinico Tor Vergata, University of Rome "Tor Vergata", viale Oxford 81, 00133, Rome, Italy.
Emanuele Luca GinevraMemory Clinic and Neurodegenerative Dementia Research Unit, Policlinico Tor Vergata, University of Rome "Tor Vergata", viale Oxford 81, 00133, Rome, Italy.
Marzia NuccetelliDepartment of Clinical Biochemistry and Molecular Biology, Policlinico Tor Vergata, University of Rome "Tor Vergata", viale Oxford 81, 00133, Rome, Italy.
Sergio BernardiniDepartment of Clinical Biochemistry and Molecular Biology, Policlinico Tor Vergata, University of Rome "Tor Vergata", viale Oxford 81, 00133, Rome, Italy.
Diego CentonzeIRCCS Neuromed, via Atinense 18, 86077, Pozzilli, IS, Italy.
Alessandro MartoranaMemory Clinic and Neurodegenerative Dementia Research Unit, Policlinico Tor Vergata, University of Rome "Tor Vergata", viale Oxford 81, 00133, Rome, Italy.
Caterina MottaMemory Clinic and Neurodegenerative Dementia Research Unit, Policlinico Tor Vergata, University of Rome "Tor Vergata", viale Oxford 81, 00133, Rome, Italy. caterina.motta@ptvonline.it.ORCID http://orcid.org/0000-0001-6734-6979

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionAnti-amyloid monoclonal antibodies have increased the need for scalable, minimally invasive biomarkers for Alzheimer's disease (AD). In this single-center cohort study, we evaluated plasma biomarkers performance in detecting biologically defined AD, assessing diagnostic accuracy and generalizability outside dedicated laboratory settings and exploring suitability for clinical implementation.

methodsWe enrolled 204 outpatients referred to the memory clinic of Policlinico "Rome Tor Vergata" who underwent standard work-up, lumbar puncture for cerebrospinal fluid (CSF) biomarkers and paired blood sampling. Among plasma biomarkers, phosphorylated tau (p-tau) 181, p-tau217, and their ratios adjusted for Aβ42 were measured on the Lumipulse platform. AD pathology was defined by CSF p-tau181/Aβ42 ≥ 0.069. ROC analyses estimated AUCs, and a two-cut-off approach targeting 90% sensitivity and specificity classified individuals as low, intermediate, or high AD risk. Subgroup analyses examined the impact of sex, age (< 75, ≥ 75 years), chronic kidney disease, and cognitive impairment (MMSE ≥ 26/30, < 26/30) on plasma biomarker levels.

resultsAmong single analytes, plasma p-tau217 showed the highest discriminative capacity (AUC 0.883). Combined ratios improved overall performance (p-tau181/Aβ42, AUC 0.928; p-tau217/Aβ42, AUC 0.894) and reduced intermediate-risk classifications to < 15%, with slightly better performance in women, patients < 75 and cognitively unimpaired. The two-cut-off model improved accuracy and rule-in ability. DISCUSSION: Plasma p-tau/Aβ42 ratios show high and robust accuracy for detecting CSF-defined AD pathology. A two-step approach based on p-tau181/Aβ42 or p-tau217/Aβ42 could streamline diagnostic workflows in memory clinics, reserving second-line assessments to indeterminate cases and supporting selection of candidates for disease-modifying anti-amyloid therapies.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesPeptide Fragmentstau ProteinsAgedAged, 80 and overBiomarkersCohort StudiesFemaleHumansMaleMiddle AgedPhosphorylationSensitivity and SpecificityAmyloid beta-Peptidesamyloid beta-protein (1-42)BiomarkersMAPT protein, humanPeptide Fragmentstau ProteinsAlzheimer’s diseaseBlood-based biomarkersPlasma combined ratiosPlasma phosphorylated tauReal-world clinical implementation

Identifiers

PMID42101517
PMCPMC13156155

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.