Brief update on different roles of tau in neurodegeneration

Both Alzheimer's disease (AD) and almost every second case of frontotemporal lobar degeneration (FTLD) are characterized by the deposition of hyperphosphorylated forms of the microtubule-associated protein tau in neurons and/or glia. This unifying pathology led to coining the umbrella term "tauopathies" for these conditions. While the deposition of tau ultimately results in the formation of typical histopathological lesions, such as the neurofibrillary tangles (NFTs) in AD, it is now well accepted that tau interferes with normal functions in neurons already before its deposition. Together with the identification of pathogenic mutations in the tau-encoding gene MAPT in FTLD and evidence from a rising number of in vivo animal models a central role of tau in neurodegeneration has emerged. Here, we review the role of pathological tau in axonal transport, mitochondrial respiration, and in mediating amyloid-β toxicity in AD. Furthermore, we review recent findings regarding the spreading of tau pathology throughout the brain as disease progresses.