Seeding activity of skin misfolded tau as a biomarker for tauopathies
Abstract 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 p...
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BMC
2024-11-01
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| Series: | Molecular Neurodegeneration |
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| Online Access: | https://doi.org/10.1186/s13024-024-00781-1 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Zerui Wang |
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| description | Abstract 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 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. |
| format | Article |
| id | doaj-art-1fa0ff5660ca40fa87bdb880b0cf5a95 |
| institution | Kabale University |
| issn | 1750-1326 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
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| series | Molecular Neurodegeneration |
| spelling | doaj-art-1fa0ff5660ca40fa87bdb880b0cf5a952024-12-01T12:44:49ZengBMCMolecular Neurodegeneration1750-13262024-11-0119111910.1186/s13024-024-00781-1Seeding activity of skin misfolded tau as a biomarker for tauopathiesZerui Wang0Ling Wu1Maria Gerasimenko2Tricia Gilliland3Zahid Syed Ali Shah4Evalynn Lomax5Yirong Yang6Steven A. Gunzler7Vincenzo Donadio8Rocco Liguori9Bin Xu10Wen-Quan Zou11Department of Pathology, Case Western Reserve University School of MedicineBiomanufacturing Research Institute and Technology Enterprise, North Carolina Central UniversityDepartment of Pathology, Case Western Reserve University School of MedicineDepartment of Pathology, Case Western Reserve University School of MedicineDepartment of Pathology, Case Western Reserve University School of MedicineDepartment of Pathology, Case Western Reserve University School of MedicineInstitute of Neurology, Department of Neurology, Jiangxi Academy of Clinical Medical Sciences, Rare Disease Center, Key Laboratory of Rare Neurological Diseases of Jiangxi Province Health Commission, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityNeurological Institute, University Hospitals Cleveland Medical CenterIRCCS Institute of Neurological Sciences of Bologna, UOC Clinica NeurologicaIRCCS Institute of Neurological Sciences of Bologna, UOC Clinica NeurologicaBiomanufacturing Research Institute and Technology Enterprise, North Carolina Central UniversityDepartment of Pathology, Case Western Reserve University School of MedicineAbstract 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 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.https://doi.org/10.1186/s13024-024-00781-1TauopathiesAlzheimer’s diseaseSeeding activityTauReal-time quaking-induced conversion (RT-QuIC)Skin |
| spellingShingle | 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 Seeding activity of skin misfolded tau as a biomarker for tauopathies Molecular Neurodegeneration Tauopathies Alzheimer’s disease Seeding activity Tau Real-time quaking-induced conversion (RT-QuIC) Skin |
| title | Seeding activity of skin misfolded tau as a biomarker for tauopathies |
| title_full | Seeding activity of skin misfolded tau as a biomarker for tauopathies |
| title_fullStr | Seeding activity of skin misfolded tau as a biomarker for tauopathies |
| title_full_unstemmed | Seeding activity of skin misfolded tau as a biomarker for tauopathies |
| title_short | Seeding activity of skin misfolded tau as a biomarker for tauopathies |
| title_sort | seeding activity of skin misfolded tau as a biomarker for tauopathies |
| topic | Tauopathies Alzheimer’s disease Seeding activity Tau Real-time quaking-induced conversion (RT-QuIC) Skin |
| url | https://doi.org/10.1186/s13024-024-00781-1 |
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