title: Tauopathies as clinicopathological entities.
abstract: Tauopathies are a class of neurodegenerative disorders characterized by neuronal and/or glial inclusions composed of the microtubule-binding protein, tau. Several lines of evidence suggest tau aggregation is central to the neurodegenerative process in tauopathies. First, recent animal and cell model studies find abnormally-modified tau alone may be transmitted between adjacent neurons and spread to anatomically connected brain regions to recapitulate human disease. Further, staging efforts in human autopsy cases suggest a sequential distribution of tau aggregation in the central nervous system that could reflect this observed cell-to-cell transmission of pathogenic tau species in animal models. Finally, pathogenic mutations in the MAPT gene encoding tau protein cause hereditary forms of tauopathy. Clinically, tauopathies can present with a range of phenotypes that include both movement- and cognitive/behavioral-disorders (i.e. frontotemporal dementia spectrum disorders) or non-specific amnestic symptoms in advanced age. A major limitation is that current clinical diagnostic criteria for these disorders do not reliably differentiate underlying tauopathy from other neurodegenerative diseases, such as TDP-43 proteinopathies. Thus, current research efforts are focused on improving the ante mortem diagnosis of tauopathies, including pre-clinical stages of disease, as many therapeutic strategies for emerging disease-modifying therapies focus on preventing abnormal folding and spread of tau pathology.
authors.affiliation: Department of Neurology, Frontotemporal Degeneration Center (FTDC), University of Pennsylvania Perelman School of Medicine, Hospital of the University of Pennsylvania, 3600 Spruce Street, Philadelphia, PA 19104, United States. Electronic address: dirwin@mail.med.upenn.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Irwin
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D020774:Pick Disease of the Brain / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D024801:Tauopathies / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C000598624:TARDBP protein, human; D016875:tau Proteins
keywords: Argyrophilic grain disease; Corticobasal degeneration; Corticobasal syndrome tauopathy; Frontotemporal dementia; Frontotemporal lobar degeneration; MAPT mutation; Pick's disease; Primary age related tauopathy; Primary progressive aphasia; Progressive supranuclear palsy