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Protocols for Monitoring the Development of Tau Pathology in Alzheimer’s Disease

  • Alberto Rábano
  • Raquel Cuadros
  • Paula Merino-Serráis
  • Izaskun Rodal
  • Ruth Benavides-Piccione
  • Elena Gómez
  • Miguel Medina
  • Javier DeFelipe
  • Jesús AvilaEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1303)

Abstract

The microtubule-associated protein tau plays a critical role in the pathogenesis of Alzheimer’s disease (AD) and several related disorders collectively known as tauopathies. Development of tau pathology is associated with progressive neuronal loss and cognitive decline. In the brains of AD patients, tau pathology spreads following a predictable, anatomically defined progression pattern that can be followed by immunohistochemistry looking at brain post-mortem samples from Alzheimer patients at different stages of the disease. Furthermore, since it has been proposed that AD may be a synaptopathy and dendritic spines of pyramidal neurons are the major targets of cortical synapses, the analysis of dendritic spines is a useful tool to study the correlation between tau phosphorylation at specific sites, synaptopathy and cognitive impairment. Finally, characterization of phosphorylated tau in detergent-insoluble protein aggregates could also be an indication of the neuropathological staging in AD. Here, we describe these three complementary protocols to follow the development of tau pathology in Alzheimer’s disease.

Key words

Dendritic spines Detergent-insoluble aggregates Gallyas stain Hyperphosphorylation Immunohistochemistry Intracellular injections Neurofibrillary degeneration Neuropathology Staging Synaptopathy Tau 

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Alberto Rábano
    • 1
  • Raquel Cuadros
    • 2
    • 3
  • Paula Merino-Serráis
    • 3
    • 4
  • Izaskun Rodal
    • 1
  • Ruth Benavides-Piccione
    • 3
    • 4
  • Elena Gómez
    • 1
  • Miguel Medina
    • 3
  • Javier DeFelipe
    • 3
    • 4
  • Jesús Avila
    • 2
    • 3
    Email author
  1. 1.Departamento de Neuropatología y Banco de TejidosFundación CIENMadridSpain
  2. 2.Centro de Biología Molecular Severo Ochoa CSIC-UAMUniversidad Autónoma de MadridMadridSpain
  3. 3.CIBERNED (Centro de Investigación en Red sobre Enfermedades Neurodegenerativas)MadridSpain
  4. 4.Laboratorio Cajal de Circuitos Corticales (CTB), UPMCampus Montegancedo and Instituto Cajal (CSIC)MadridSpain

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