Seeding Activity of Skin Misfolded Proteins as a Biomarker in Prion and Prion-Like Diseases

Zou, Wen-Quan; Wang, Zerui

doi:10.1007/978-3-031-20565-1_32

Cited by 2 publications

(1 citation statement)

References 118 publications

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“…The ultrasensitive technology termed seed-amplification assay (SAA) of misfolded proteins by either real time quaking-induced conversion (RT-QuIC) or protein misfolding cyclic amplification assay (PMCA) has made it possible to identify new biomarkers in easily accessible specimens for early diagnosis and assessment of disease progression [36, 41, 57]. It has been widely used in the detection not only of prions but also other prion-like misfolded proteins such as αSyn and tau in body fluids and peripheral tissues of PrD and PD by detecting the seeding activity (SA) of misfolded proteins [4, 14, 18, 39, 40, 47, 50].…”

Section: Introductionmentioning

confidence: 99%

Seeding Activity of Skin Misfolded Tau as a Novel Biomarker for Tauopathies

Wang,

Wu,

Gerasimenko

et al. 2023

Preprint

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Tauopathies are a group of age-related neurodegenerative diseases with a molecular hallmark of the prion-like propagation and accumulation of pathologically phosphorylated tau protein in the brain. They include Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick’s disease (PiD). Currently, in the peripheral tissues and body fluids there are no reliable diagnostic biomarkers available that are able to directly reflect the capability of propagation and spreading of the misfolded tau aggregates. Here, we revealed significantly increased amounts of phosphorylated tau in the skin of AD patients compared to those in other tauopathies and normal controls. Moreover, the seed-amplification assay (SAA) by the ultrasensitive real-time quaking-induced conversion (RT-QuIC) displayed that the prion-like seeding activity of pathological tau in the skin of cadavers with neuropathologically confirmed tauopathies including AD, PSP, CBD, PiD was dramatically higher than that in normal controls, yielding 75-80% sensitivity and 95-100% specificity, respectively, depending on different tau substrates used. The increased tau-seeding activity was also observed in biopsy skin samples from living AD and PSP patients. Moreover, analysis of the end products of skin-tau SAA confirmed that the increased seeding activity is accompanied with formation of tau aggregates that are of different physicochemical properties determined by the different tau-substrates used. Our study provides proof-of-concept that the skin tau-SAA can differentiate tauopathies from normal controls, suggesting that the seeding activity of the skin misfolded tau can serve as an accurate diagnostic biomarker of tauopathies.

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Section: Introductionmentioning

confidence: 99%

Seeding Activity of Skin Misfolded Tau as a Novel Biomarker for Tauopathies

Wang,

Wu,

Gerasimenko

et al. 2023

Preprint

Self Cite

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Seeding Activity of Skin Misfolded Tau as a Biomarker for Tauopathies

Wang,

Wu,

Gerasimenko

et al. 2024

Preprint

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Background Tauopathies are a group of age-related neurodegenerative diseases characterized by the accumulation of pathologically phosphorylated tau protein in the brain, leading to prion-like propagation and aggregation. 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 prion-SAA demonstrated a significantly higher sensitivity (75–80%) and specificity (95–100%) for detecting tauopathy, depending on the tau substrates used. Moreover, 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 can differentiate tauopathies from normal controls, suggesting that the seeding activity of misfolded tau in the skin could serve as a diagnostic biomarker for tauopathies.

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Seeding Activity of Skin Misfolded Proteins as a Biomarker in Prion and Prion-Like Diseases

Cited by 2 publications

References 118 publications

Seeding Activity of Skin Misfolded Tau as a Novel Biomarker for Tauopathies

Seeding Activity of Skin Misfolded Tau as a Novel Biomarker for Tauopathies

Seeding Activity of Skin Misfolded Tau as a Biomarker for Tauopathies

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