Tau is a heterogeneous microtubule-associated protein that promotes and stabilizes microtubule assembly, especially in axons. Phosphorylation decreases the ability of tau to bind to microtubules. Neurofibrillary tangles are a major hallmark of Alzheimer's disease; these tangles are bundles of paired helical filaments composed of hyperphosphorylated tau. Tau is found to be the major component of the paired helical filaments (PHFs) found in the brains of patients with Alzheimer disease (AD). Tau is hyperphosphorylated in PHFs, and specific phosphorylation sites have been implicated in the loss of Taus association with the membrane cortex during AD disease state.