Acs Chem Neurosci
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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. ⋯ 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.