title: Protocols for Monitoring the Development of Tau Pathology in Alzheimer's Disease.
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.
authors.affiliation: Departamento de Neuropatología y Banco de Tejidos, Fundación CIEN, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Rábano
authors.forename: Raquel
authors.initials: R
authors.lastname: Cuadros
authors.forename: Paula
authors.initials: P
authors.lastname: Merino-Serráis
authors.forename: Izaskun
authors.initials: I
authors.lastname: Rodal
authors.forename: Ruth
authors.initials: R
authors.lastname: Benavides-Piccione
authors.forename: Elena
authors.initials: E
authors.lastname: Gómez
authors.forename: Miguel
authors.initials: M
authors.lastname: Medina
authors.forename: Javier
authors.initials: J
authors.lastname: DeFelipe
authors.forename: Jesús
authors.initials: J
authors.lastname: Avila
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications*; D015153:Blotting, Western / Q000379:methods*; D001921:Brain / Q000473:pathology / Q000648:ultrastructure; D049229:Dendritic Spines / Q000378:metabolism / Q000473:pathology; D003902:Detergents / Q000737:chemistry; D005260:Female; D006801:Humans; D007120:Immunochemistry / Q000379:methods*; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission; D010766:Phosphorylation; D066329:Protein Aggregates; D017966:Pyramidal Cells / Q000473:pathology; D016622:Silver Staining; D012995:Solubility; D024801:Tauopathies / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D016707:Tissue Fixation; D016875:tau Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D003902:Detergents; D066329:Protein Aggregates; D016875:tau Proteins