NeuralCipher Research overview
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Abstract Parkinson's disease (PD) is neuropathologically defined by α‑synuclein (αSyn) aggregation, yet nearly half of patients exhibit comorbid tau-pathology indicated by neuropathological examination. Using skin RT‑QuIC and plasma biomarkers [p‑tau217, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL)], we assessed αSyn- and tau-seeding across independent PD cohorts. αSyn‑seeding demonstrated robust diagnostic performance, discriminating PD from controls with ~ 90–95% sensitivity and specificity. Surprisingly, 40–50% of PD patients showed positive skin tau‑seeding; however, all PD subgroups, regardless of tau status, displayed plasma p‑tau217 and GFAP levels indistinguishable from controls, starkly contrasting with Alzheimer's disease (AD) where marked elevations occurred. Skin tau correlated with plasma p‑tau217 in AD, but not in PD, and tau fibrils from PD were morphologically distinct from AD. Thus, skin tau-seeding in PD may reflect a non‑AD tauopathy independent of classical biomarkers, challenging diagnostic assumptions and underscoring the need for multimodal strategies to guide personalized stratification.
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