Abstract
Pathological studies show that neurofibrillary tangles are found in regions where neuronal death occurs. This observation raises the question: Are neurofibrillary tangles toxic or protective? Findings from various mouse models expressing human tau with the FTDP17 mutation suggest that some component involved in the formation of neurofibrillary tangles, rather than the neurofibrillary tangles themselves, might be responsible for the toxicity leading to neuronal death. Here, I review our current understanding of a toxic species of tau and the mechanism by which it contributes to neuronal dysfunction and death. Recent studies suggest that, before forming fibrils but after becoming hyperphosphorylated, tau is involved in neurodegenerative disease.