--- - |2 Summary Alzheimer's disease (AD) is a neurodegenerative disorder with an incompletely defined aetiology that is associated with memory and cognitive impairment. Currently available therapeutics only provide temporary assistance with symptoms. In spite of plentiful research in the field and the generation of thousands of studies, much is still to be clarified on precise mechanisms of pathobiology, prevention modalities, disease course and cure. Netrin‐1, a laminin family protein, is said to have anti‐inflammatory and anti‐apoptotic effects and has a key role in neurogenesis and morphogenesis of neural structures. Accordingly, this study was designed to investigate protective effects of bilateral intrahippocampal fissure microinjections of netrin‐1 on memory impairment in rat model of AD. Concomitant administration of netrin‐1 with amyloid beta 1‐42 (Aβ1‐42) improved cognitive dysfunction in novel object recognition task (NOR), ameliorated impaired spatial memory in Morris water maze (MWM) setting, increased neuronal density and reduced amyloid aggregation in rat AD model. Netrin‐1 was also seen to prevent Aβ1‐42‐induced caspase‐3, caspase‐7 and NF‐κB (nuclear factor kappa‐light‐chain‐enhancer of activated B cells) activation. Therefore, based on the data reported here, netrin‐1 may be a promising biologic therapeutic that addresses the memory and neuronal loss associated with AD. - 'Clinical and Experimental Pharmacology and Physiology, EarlyView. '