APP and Brain atrophy: AD is a devastating progressive neurodegenerative disease characterized by cognitive decline, brain atrophy due to neuronal and synapse loss, and two neuropathological lesions firstly described by Alois Alzheimer in 1907: extracellular amyloid plaques and neurofibrillary tangles formation, composed of amyloid-beta peptide (Aβ) and intracellular aggregates of hyperphosphorylated tau protein, respectively (Goedert and Spillantini, 2006).