MAPT and Alzheimer disease: The most likely explanation for these failures is that AD multifaceted and is caused by inter-related cellular, biochemical and molecular abnormalities that culminate in loss of neurons, deposition of amyloid beta, accumulation of phospho-tau-containing neuronal cytoskeletal lesions, activation of cell death cascades, deficits in energy metabolism, mitochondrial dysfunction, increased inflammation, DNA damage and oxidative stress.