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4-Repeat tau seeds and templating subtypes as brain and CSF biomarkers of frontotemporal lobar degeneration.
Saijo, Eri; Metrick, Michael A; Koga, Shunsuke; Parchi, Piero; Litvan, Irene; Spina, Salvatore; Boxer, Adam; Rojas, Julio C; Galasko, Douglas; Kraus, Allison; Rossi, Marcello; Newell, Kathy; Zanusso, Gianluigi; Grinberg, Lea T; Seeley, William W; Ghetti, Bernardino; Dickson, Dennis W; Caughey, Byron.
Afiliación
  • Saijo E; LPVD, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT, USA.
  • Metrick MA; LPVD, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT, USA.
  • Koga S; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
  • Parchi P; IRCCS Istituto delle Scienze Neurologiche di Bologna, 40139, Bologna, Italy.
  • Litvan I; Department of Experimental Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40138, Bologna, Italy.
  • Spina S; Department of Neurosciences, Parkinson and Other Movement Disorders Center, University of California, San Diego, CA, USA.
  • Boxer A; Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
  • Rojas JC; Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
  • Galasko D; Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
  • Kraus A; Department of Neurosciences, University of California, San Diego, CA, USA.
  • Rossi M; LPVD, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT, USA.
  • Newell K; IRCCS Istituto delle Scienze Neurologiche di Bologna, 40139, Bologna, Italy.
  • Zanusso G; Indiana University School of Medicine, Indianapolis, IN, USA.
  • Grinberg LT; University of Verona, Verona, Italy.
  • Seeley WW; Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
  • Ghetti B; Department of Pathology, LIM-22, University of Sao Paulo, Sao Paulo, Brazil.
  • Dickson DW; Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
  • Caughey B; Indiana University School of Medicine, Indianapolis, IN, USA.
Acta Neuropathol ; 139(1): 63-77, 2020 01.
Article en En | MEDLINE | ID: mdl-31616982
To address the need for more meaningful biomarkers of tauopathies, we have developed an ultrasensitive tau seed amplification assay (4R RT-QuIC) for the 4-repeat (4R) tau aggregates of progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and other diseases with 4R tauopathy. The assay detected seeds in 106-109-fold dilutions of 4R tauopathy brain tissue but was orders of magnitude less responsive to brain with other types of tauopathy, such as from Alzheimer's disease cases. The analytical sensitivity for synthetic 4R tau fibrils was ~ 50 fM or 2 fg/sample. A novel dimension of this tau RT-QuIC testing was the identification of three disease-associated classes of 4R tau seeds; these classes were revealed by conformational variations in the in vitro amplified tau fibrils as detected by thioflavin T fluorescence amplitudes and FTIR spectroscopy. Tau seeds were detected in postmortem cerebrospinal fluid (CSF) from all neuropathologically confirmed PSP and CBD cases but not in controls. CSF from living subjects had weaker seeding activities; however, mean assay responses for cases clinically diagnosed as PSP and CBD/corticobasal syndrome were significantly higher than those from control cases. Altogether, 4R RT-QuIC provides a practical cell-free method of detecting and subtyping pathologic 4R tau aggregates as biomarkers.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biomarcadores / Fluoroinmunoensayo / Proteínas tau / Degeneración Lobar Frontotemporal Tipo de estudio: Diagnostic_studies Límite: Humans Idioma: En Revista: Acta Neuropathol Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biomarcadores / Fluoroinmunoensayo / Proteínas tau / Degeneración Lobar Frontotemporal Tipo de estudio: Diagnostic_studies Límite: Humans Idioma: En Revista: Acta Neuropathol Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania