ABSTRACT
Tau is one of the major proteins that contributes to the neuropathology of Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), and other neurodegenerative diseases with neurofibrillary tangles (NFT). Recent studies have demonstrated that some of the FTDP-17 mutations in tau either increase expression of tau protein isoforms with four microtubule binding sites (4R tau), or reduce the binding of tau to microtubules.1-3 Most importantly, these mutations in tau lead to the formation of NFT and neuronal degeneration. However, the mechanisms underlying the polymerization of tau protein into straight and paired helical filaments (PHF) and the formation of stable NFT in tauopathies are unclear. We hypothesize that cross-linking of tau protein by transglutaminase stabilizes tau microfilaments and thereby promotes their aggregation into NFT in tauopathies.
