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Simple, Single-Shot Phosphoproteomic Analysis of Heat-Stable Tau Identifies Age-Related Changes in pS235- and pS396-Tau Levels in Non-human Primates.
Leslie, Shannon N; Kanyo, Jean; Datta, Dibyadeep; Wilson, Rashaun S; Zeiss, Caroline; Duque, Alvaro; Lam, TuKiet T; Arnsten, Amy F T; Nairn, Angus C.
Afiliación
  • Leslie SN; Department of Psychiatry, Yale School of Medicine, Yale University, New Haven, CT, United States.
  • Kanyo J; Interdepartmental Neuroscience Program, Yale School of Medicine, Yale University, New Haven, CT, United States.
  • Datta D; Keck MS & Proteomics Resource, Yale School of Medicine, Yale University, New Haven, CT, United States.
  • Wilson RS; Department of Neuroscience, Yale School of Medicine, Yale University, New Haven, CT, United States.
  • Zeiss C; Keck MS & Proteomics Resource, Yale School of Medicine, Yale University, New Haven, CT, United States.
  • Duque A; Department of Comparative Medicine, Yale School of Medicine, Yale University, New Haven, CT, United States.
  • Lam TT; Department of Neuroscience, Yale School of Medicine, Yale University, New Haven, CT, United States.
  • Arnsten AFT; Keck MS & Proteomics Resource, Yale School of Medicine, Yale University, New Haven, CT, United States.
  • Nairn AC; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, United States.
Front Aging Neurosci ; 13: 767322, 2021.
Article en En | MEDLINE | ID: mdl-34867294
Age is the most significant risk factor for Alzheimer's disease (AD), and understanding its role in specific aspects of AD pathology will be critical for therapeutic development. Neurofibrillary tangles composed of hyperphosphorylated tau are a quintessential hallmark of AD. To study age-related changes in tau phosphorylation, we developed a simple, antibody-free approach for single shot analysis of tau phosphorylation across the entire protein by liquid-chromatography tandem mass spectrometry. This methodology is species independent; thus, while initially developed in a rodent model, we utilized this technique to analyze 36 phosphorylation sites on rhesus monkey tau from the prefrontal cortex (PFC), a region vulnerable to AD-linked degeneration. Data are available via ProteomeXchange with identifier PXD027971. We identified novel, age-related changes in tau phosphorylation in the rhesus monkey PFC and analyzed patterns of phosphorylation change across domains of the protein. We confirmed a significant increase and positive correlation with age of phosphorylated serine 235 tau and phosphorylated serine 396 tau levels in an expanded cohort of 14 monkeys. Histology showed robust labeling for tau phosphorylated at these sites in vulnerable layer III pyramidal cells in the PFC. The results presented in this study suggest an important role of the natural aging process in tau phosphorylation in rhesus monkey.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Front Aging Neurosci Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Front Aging Neurosci Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza