The calcium/calmodulin‑dependent protein kinase kinase 2, adenosine monophosphate‑activated protein kinase (CAMKK2‑AMPK) pathway mediated amyloid β42 (Aβ42)‑induced synaptotoxicity and blockage of CAMKK2‑protected neurons against the effect of Aβ42. Numerous microRNAs (miRNAs) were downregulated in response to Aβ42, including miR‑9, a synapse‑enriched miRNA that is decreased in Alzheimer's disease. In the present study the effect of miR‑9 on Aβ42‑triggered CAMKK2‑AMPK activation and the synaptotoxic impairment was investigated. Aβ42 oligomers were identified to be capable of inducing CAMKK2‑AMPK pathway activation, which was attenuated by miR‑9 overexpression. CAMKK2 was predicted to be a target of miR‑9 using Pictar and Targetscan 6.2 Bioinformatics' algorithms. A luciferase activity assay and western blot analysis confirmed that miR‑9 significantly inhibited CAMKK2 expression. Additionally, overexpression of miR‑9 was sufficient to restore Aβ42‑induced dendritic spine loss and rescued Aβ42‑induced τ phosphorylation at Ser‑262 mediated by the CAMKK2‑AMPK pathway. The results of the present study demonstrated that miR‑9 attenuated Aβ‑induced synaptotoxicity by targeting CAMKK2.