Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive amyloid-β (Aβ) accumulation， neurofibrillary tangles (NFTs) formation and synaptic alterations. Active immunotherapy is regarded as one of the most promising strategies for AD prevention and treatment. In this research， we used APPswe/PS1M146 V/TauP301 L triple transgenic (3×Tg-AD) mice， in which the pathological changes are the most similar to those in AD patients. The Aβ 3-10 -keyhole limpet haemocyanin (KLH) vaccine was administered to mice at 1 month， and no AD-associated changes were detected at that time. The vaccine effectively mitigated AD-like pathology and cognitive dysfunction in the 3×Tg-AD mice. Both soluble and insoluble Aβ and tau protein in the brain tissues of the 3×Tg-AD mice were significantly decreased after the administration of Aβ 3-10 -KLH. In addition， the level of phosphorylated tau also decreased following removal of the Aβ pathological changes.