Nogo-A is a protein inhibiting axonal regeneration, which is considered a major obstacle to nerve regeneration after injury in mammals. Rapid progress has been achieved in new physiopathological function of Nogo-A in Alzheimer's disease in the past decade. Recent research shows that through binding to Nogo-A receptor, Nogo-A plays an important role in Alzheimer's disease (AD) pathogenesis. Particularly, Nogo-A/Nogo-A receptors modulate the generation of amyloid β-protein (Aβ), which is thought to be a major cause of AD. This review describes the recent development of Nogo-A, Nogo-A receptor, and downstream signaling involved in AD and pharmacological basis of therapeutic drugs. We concluded the Nogo-A/Nogo-A receptor provide new insight into potential mechanisms and promising therapy strategies in AD.