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

Abstract

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