Here, we found that the microRNA-485-3p (miR-485-3p) was overexpressed in the brain tissues and cerebrospinal fluid (CSF) of patients with AD, and its antisense oligonucleotide (ASO) reduced Aβ plaque accumulation, tau pathology development, neuroinflammation, and cognitive decline in a transgenic mouse model of AD. This evidence concerns the gene MAPT and Alzheimer disease.