Familial AD (fAD) and sAD share many neuropathological features, including Aβ accumulation and toxicity, tau hyperphosphorylation, oxidative stress, neuroinflammation, cholinergic neuronal degeneration, activation of apoptotic pathways, insulin desensitization/resistance state, synapse alteration and autophagy dysfunction. Here, MAPT is linked to familial Alzheimer disease.