title: The role of tau oligomers in the onset of Alzheimer's disease neuropathology.
abstract: Most neurodegenerative diseases are characterized by the presence of protein aggregates. Alzheimer's disease (AD) is the most common cause of dementia in people over age 60. One of the histopathological hallmarks of AD is the presence of tau protein aggregates. Historically, it has been thought that paired helical filaments (PHFs) were the toxic form of tau that assembled to form neurofibrillary tangles (NFTs), but recently there has been evidence that tau oligomers, which form before PHFs and NFTs, could be the structures mediating neurodegeneration even before the fibrillary tau is deposited. Here, we discuss the recent advances in tau oligomer research, their implications on AD and other tauopathies, the mechanisms of tau turnover by the principal protein clearance systems (the proteasome and autophagy), and the potential use of tau oligomers as drug targets for the development of new therapeutic approaches.
authors.affiliation: Molecular Biomedicine Department, CINVESTAV-IPN , Ave. Politécnico 2508, Colonia San Pedro Zacatenco, México City, D.F. 07360, México.
authors.forename: María del Carmen
authors.initials: Mdel C
authors.lastname: Cárdenas-Aguayo
authors.forename: Laura
authors.initials: L
authors.lastname: Gómez-Virgilio
authors.forename: Steven
authors.initials: S
authors.lastname: DeRosa
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Meraz-Ríos
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D016875:tau Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D016875:tau Proteins
keywords: Alzheimer’s disease; Tau oligomers; aggregation; autophagy; neurodegeneration; new drug targets; proteasome; protein spreading; synaptic impairment