Plasma tau-species-positive neuron-derived extracellular vesicles in progressive supranuclear palsy.

Plasma neuron-derived extracellular vesicles carrying tau species distinguish progressive supranuclear palsy from Parkinson’s disease and healthy controls, with AUCs up to 0.990 in validation.

• Why it matters: Early PSP diagnosis is difficult, especially separating it from PD, and a peripheral biomarker reflecting CNS pathology is needed.
• What they did: In 188 participants across three centres, plasma NDEVs were profiled by nano-scale flow cytometry for total tau, 4R tau, and phosphorylated tau (ptau181, ptau217, ptau231, ptau396), then logistic models were trained in discovery and strictly validated.
• The result: In the validation cohort, tau-, 4R tau-, ptau181-, ptau217-, and ptau396-containing NDEVs were higher in PSP than HCs, and tau-, 4R tau-, ptau181-, and ptau217-containing NDEVs were higher in PSP than PD; integrated AUCs were 0.971 (PSP vs HCs) and 0.990 (PSP vs PD), including 0.987 for early-stage PSP vs PD.

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