Tau is a neuronal microtubule-associated protein that stabilizes axonal microtubules by binding with them. If tau proteins get phosphorilated, they are separated from microtubules, and they form paired helical filaments in the neuronal cytoplasm. Neurofibrillary tangles are abnormal intracellular aggregates of bundles of 12-kDa protein consisting of the residual microtubule-binding sites of tau protein after the truncation of the N- and C-terminal domains. Although it is not clearly known whether beta-amyloid plays a role in the formation of neurofibrillary tangles, a study has reported that the injection beta-amyloid42 into the brain of a tau-transgenic mouse resulted in a 5-fold   increase in the formation of neurofibrillary tangles that was elicited by an increase of tau phosphorylation.