title: The role of tau in Alzheimer's disease.
abstract: Despite earlier uncertainties about the role of tau pathology in AD, the discovery of multiple mutations in the tau gene that lead to the abnormal aggregation of tau and the onset/progression of FTDP-17 demonstrates that tau dysfunction is sufficient to produce neurodegenerative disease. The mutations lead to specific cellular alterations, including altered expression, function and biochemistry of tau. The finding that specific tau gene mutations lead to diverse FTDP-17 phenotypes raises the possibility that the clinical and pathological expression of hereditary and related sporadic tauopathies may be influenced by tau gene polymorphisms, other genetic factors and epigenetic events. However, the precise mechanisms whereby tau assembles into filaments and causes neurodegeneration in the human brain remain to be elucidated, but further investigation into the mechanisms of tau dysfunction, as well as the identification of potential disease-modifying factors, will provide additional insight into novel strategies for the treatment and prevention of AD and related disorders. Moreover, development of additional animal models of tauopathies that more closely recapitulate human diseases will facilitate this undertaking, and this is likely to have implications for other neurodegenerative disorders since the aggregation of tau in AD and and related tauopathies is an example of abnormal protein-protein interactions resulting in the intracellular accumulation of filamentous proteins that is a common feature of many fatal CNS diseases characterized by relentlessly progressive brain degeneration [1-3]. Thus, the fibrillization and aggregation of proteins in the brain is a common theme in a diverse group of neurodegenerative disorders and insight into the pathogenesis of any one of these disorders may have implications for understanding the mechanisms that underlie all these diseases as well as for the discovery of better strategies to treat them [1-3].
authors.affiliation: Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Maloney Building, 3rd Floor, HUP, Philadelphia, PA 19104, USA. trojanow@mail.med.upenn.edu
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: Virginia M Y
authors.initials: VM
authors.lastname: Lee
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D006801:Humans; D024801:Tauopathies / Q000473:pathology*; D016875:tau Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D016875:tau Proteins