In the preclinical stages of AD, there is also an aberrant deposition of misfolded proteins, called extracellular amyloid β plaques (Aβ) and intracellular tau-based neurofibrillary tangles, which contribute to the pathogenesis of brain atrophic lesions and, hence, cognitive deterioration (Figure 2A) (40, 43). The gene discussed is MAPT; the disease is Alzheimer disease.