Seeding activity of skin misfolded tau as a biomarker for tauopathies

作者：Zerui Wang, Ling Wu, Maria Gerasimenko, Tricia Gilliland, Zahid Syed Ali Shah, Evalynn Lomax, Yirong Yang, Steven A. Gunzler, Vincenzo Donadio, Rocco Liguori, Bin Xu, Wen‐Quan Zou · 发表于：Molecular Neurodegeneration · 年份：2024 · DOI：10.1186/s13024-024-00781-1 · 被引用次数：31 · 研究领域：Alzheimer's disease research and treatments、Dementia and Cognitive Impairment Research、Ginkgo biloba and Cashew Applications

BACKGROUND: Tauopathies are a group of age-related neurodegenerative diseases characterized by the accumulation of pathologically hyperphosphorylated tau protein in the brain, leading to prion-like aggregation and propagation. They include Alzheimer's disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick's disease (PiD). Currently, reliable diagnostic biomarkers that directly reflect the capability of propagation and spreading of misfolded tau aggregates in peripheral tissues and body fluids are lacking. METHODS: We utilized the seed-amplification assay (SAA) employing ultrasensitive real-time quaking-induced conversion (RT-QuIC) to assess the prion-like seeding activity of pathological tau in the skin of cadavers with neuropathologically confirmed tauopathies, including AD, PSP, CBD, and PiD, compared to normal controls. RESULTS: We found that the skin tau-SAA demonstrated a significantly higher sensitivity (75-80%) and specificity (95-100%) for detecting tauopathy, depending on the tau substrates used. Moreover, the increased tau-seeding activity was also observed in biopsy skin samples from living AD and PSP patients examined. Analysis of the end products of skin-tau SAA confirmed that the increased seeding activity was accompanied by the formation of tau aggregates with different physicochemical properties related to two different tau substrates used. CONCLUSIONS: Overall, our study provides proof-of-concept that the skin tau-SAA ca...