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Lucilla Parnetti

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Open access Jul 2026

Beyond diagnosis: can fluid tau biomarkers stage Alzheimer’s disease? Lessons from down syndrome

The introduction of blood-based biomarkers (BBMs) for Alzheimer’s disease (AD) represents one of the most transformative advances in neurodegenerative disease research over the past decade. 1,2 For the first time, biological evidence of AD pathology can be obtained through a minimally invasive, scalable blood test, opening new opportunities for early diagnosis, patient triage, and implementation of disease-modifying therapies. 3 Among the available biomarkers, phosphorylated tau (p-tau) species, particularly plasma p-tau217, have consistently shown excellent diagnostic performance across the AD continuum, recently culminating in regulatory approval of plasma p-tau217-based assays in both the USA and Europe. 4–6 Despite this remarkable clinical success, a fundamental paradox remains. Plasma tau biomarkers work

Lucilla Parnetti, L. Gaetani · 0 citations
Jul 2026

Can the integration of blood-based biomarkers into Alzheimer's disease diagnosis revolutionize the field?

INTRODUCTION Alzheimer's disease (AD) is a clinical-biological entity in which pathophysiological changes precede symptoms by years. Biomarkers are essential for early and accurate diagnosis, particularly in the era of disease-modifying therapies requiring biological confirmation. Cerebrospinal fluid (CSF) and amyloid positron emission tomography (amyloid-PET) are the reference standards, but increasing attention is devoted to blood-based biomarkers (BBMs) due to their scalability and cost-effectiveness. AREAS COVERED In this critical perspective, the authors critically appraise the current evidence supporting plasma phosphorylated tau at threonine 217 (p-tau217) as the leading BBM for AD. They also discuss its analytical performance, biological rationale, and diagnostic accuracy across the AD continuum, its relationship with established CSF, PET, and neuropathological biomarkers, its potential role in identifying patients eligible for disease-modifying therapies, and the main clinical and biological factors influencing its interpretation. Finally, they highlight current limitations, unresolved challenges, and give their future perspectives for the integration of plasma biomarkers into routine clinical practice. EXPERT OPINION BBMs are expected to reshape AD diagnostics. A stepwise approach, using plasma biomarkers as first-line tests followed by confirmatory CSF or PET, is currently the most feasible strategy. Ultimately, highly specific, brain-derived tau biomarkers may enable BBMs to replace CSF biomarkers.

L. Gaetani, Giovanna Nardi, Lucilla Parnetti · 0 citations