Accumulation of amyloid-β peptides (Aβ) proteolytically produced from amyloid precursor protein is the strong candidate of pathological cause of Alzheimer’s disease (AD). Recent studies suggest that soluble Aβ including oligomers affect synaptic function of neurons in AD pathogenesis. Although Reelin-Dab1 signal has been well studied in the context of brain morphogenesis during development, its involvement in psychiatric diseases was recently suggested from human genome studies as well as animal and biochemical experimental studies. Especially, it has been reported that the molecules of Reelin-Dab1 signal are involved in AD pathogenesis. Here, we review these studies and discuss Reelin-Dab1 signal as a possible therapeutic target of AD.