title: Tau Biology and Tau-Directed Therapies for Alzheimer's Disease.
abstract: Alzheimer's disease (AD) is characterised by a progressive loss of cognitive functions. Histopathologically, AD is defined by the presence of extracellular amyloid plaques containing Aβ and intracellular neurofibrillary tangles composed of hyperphosphorylated tau proteins. According to the now well-accepted amyloid cascade hypothesis is the Aβ pathology the primary driving force of AD pathogenesis, which then induces changes in tau protein leading to a neurodegenerative cascade during the progression of disease. Since many earlier drug trials aiming at preventing Aβ pathology failed to demonstrate efficacy, tau and microtubules have come into focus as prominent downstream targets. The article aims to develop the current concept of the involvement of tau in the neurodegenerative triad of synaptic loss, cell death and dendritic simplification. The function of tau as a microtubule-associated protein and versatile interaction partner will then be introduced and the rationale and progress of current tau-directed therapy will be discussed in the biological context.
authors.affiliation: Department of Neurobiology, University of Osnabrück, Barbarastrasse 11, 49076, Osnabrück, Germany.
authors.forename: Lidia
authors.initials: L
authors.lastname: Bakota
authors.affiliation: Department of Neurobiology, University of Osnabrück, Barbarastrasse 11, 49076, Osnabrück, Germany. brandt@biologie.uni-osnabrueck.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Brandt
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D034261:Epothilones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007116:Immunization, Passive; D008751:Methylene Blue / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D058990:Molecular Targeted Therapy; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D066263:Protein Aggregation, Pathological / Q000517:prevention & control*; D016875:tau Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D034261:Epothilones; C054369:MAPT protein, human; D009842:Oligopeptides; D016875:tau Proteins; C425904:davunetide; C114026:desoxyepothilone B; D008751:Methylene Blue