title: Tau and neurodegenerative disease: the story so far.
abstract: In 1975, tau protein was isolated as a microtubule-associated factor from the porcine brain. In the previous year, a paired helical filament (PHF) protein had been identified in neurofibrillary tangles in the brains of individuals with Alzheimer disease (AD), but it was not until 1986 that the PHF protein and tau were discovered to be one and the same. In the AD brain, tau was found to be abnormally hyperphosphorylated, and it inhibited rather than promoted in vitro microtubule assembly. Almost 80 disease-causing exonic missense and intronic silent mutations in the tau gene have been found in familial cases of frontotemporal dementia but, to date, no such mutation has been found in AD. The first phase I clinical trial of an active tau immunization vaccine in patients with AD was recently completed. Assays for tau levels in cerebrospinal fluid and plasma are now available, and tau radiotracers for PET are under development. In this article, we provide an overview of the pivotal discoveries in the tau research field over the past 40 years. We also review the current status of the field, including disease mechanisms and therapeutic approaches.
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Inge Grundke-Iqbal Research Floor, 1050 Forest Hill Road, Staten Island, New York 10314, USA.
authors.forename: Khalid
authors.initials: K
authors.lastname: Iqbal
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Inge Grundke-Iqbal Research Floor, 1050 Forest Hill Road, Staten Island, New York 10314, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Inge Grundke-Iqbal Research Floor, 1050 Forest Hill Road, Staten Island, New York 10314, USA.
authors.forename: Cheng-Xin
authors.initials: CX
authors.lastname: Gong
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D035843:Biomedical Research; D001921:Brain / Q000503:physiopathology; D004252:DNA Mutational Analysis; D057180:Frontotemporal Dementia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000473:pathology / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000235:genetics; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics; D024801:Tauopathies / Q000473:pathology / Q000503:physiopathology*; D016875:tau Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D016875:tau Proteins; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn