MAPT and early-onset autosomal dominant Alzheimer disease: Phospho-Tau (P-Tau) recognizes endogenous levels of tau protein when phosphorylated at Ser400 or Thr403 or Ser404. Studies have shown that tau phosphorylation at Ser404 destabilizes microtubules and that tau is hyperphosphorylated at Ser404 in Alzheimer’s disease (Evans et al., 2000). Phosphorylation decreases the ability of tau to bind to microtubules, destabilizing the structure and driving it toward disassembly. Neurofibrillary tangles are a major hallmark of Alzheimer’s disease; these tangles are composed of hyperphosphorylated tau (Johnson and Stoothoff, 2004).