MAPT and Alzheimer disease: Although AD is often considered a disease of gray matter, white matter (WM) degeneration is evident in adults diagnosed with clinical AD [12–14] and is also observed during the preclinical stage (i.e., prior to onset of clinical AD) and thought to result from the presence of extracellular Aβ plaques followed by intracellular neurofibrillary tangles of the protein tau [13–16].