APP and Alzheimer disease: Interestingly, we found that exercise significantly increased the protein content of CHIP in the hippocampus of APP/PS1 mice, and we speculated that this was because exercise upregulated HSP70 expression through activation of the PI3K/Akt pathway in the hippocampus of AD mice, which compensated by increasing the protein level of CHIP, which in turn formed a Tau/HSP/CHIP aggregate that was proteasomally degraded, reducing soluble phosphorylated Tau deposition and NFT formation.