MAPT and Alzheimer disease: Instead, tau mutations enhance the deposition of neurofibrillary tangles i.e. the other neuropathological hallmark of AD, but not amyloid plaques, and lead to different neuropathological disorders.3 These genetic signatures coupled with the observation that Aβ deposition precedes other biochemical and histopathological changes, including neurofibrillary tangle formation,4 provide evidence that tau aggregation occurs downstream to Aβ aggregation.