Reduction of amyloid beta by Aß3-10-KLH vaccine also decreases tau pathology in 3×Tg-AD mice.

ABSTRACT

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive amyloid-ß (Aß) 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 Aß 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 Aß and tau protein in the brain tissues of the 3×Tg-AD mice were significantly decreased after the administration of Aß 3-10 -KLH. In addition, the level of phosphorylated tau also decreased following removal of the Aß pathological changes.