Caffeoylquinic acid (CQA) is one of the phenylpropanoids found in a variety of natural resources and foods, such as sweetpotato, propolis, and coffee. Previously, we found that 3,5-di-O-caffeoylquinic acid (3,5-di-CQA, 1) and 3,4,5-tri-O-caffeoylquinic acid (3,4,5-tri-CQA, 2) possesed neuroprotective effect against amyloid-β_<1-42> (Aβ)-induced cell death. Proteomics analysis of CQA-treated cells has shown that 1 and 2 induced the oerexpression of glycolysis enzymes (phosphoglycerate kinase-1; PGK1, phosphoglycerate mutase 1; PGAM1). In this study, we investigated structure activity relationships of CQAscontaining 1 and 2 on energy generation promotion activity. Moreover, we carried out the measurement of escape latency time to find the hidden platform in Morris water maze (MWM) using senescence-accelerated-prone mice (SAMP8). To investigate the relationship between the upregulated glycolytic enzyme's effects on energy generation and the neuroprotective activity, the level of ATP on cells treated with 1 and 2 were evaluated. Intracellullar ATP level in the neuronal cells treated with compounds 1 and 2 was higher than in control cells. Intracellular ATP level in 2 treated cell was higher activity than 1 treated ell. And we checked the mRNA expression of glycolysis enzymes on treated cells with 1 and 2, respectively. As a result, the mRNA expression level of glycolysis enzyme, PGAM1, PGK1, and G3PDH, were increased by compounds 1 and 2. Additionally, we carried out the measurement of escape latency time to find the hidden platform in Morris water maze. Consequently, 1 and 2 administration induced the improvement of spatial learning and memory on SAMP8 mice, and the overexpression of PGK1 mRNA in SAMP8 brain. In this session, we also describe the recent findings about mechanism of neuroprotective activity and activation on energy metabolism by CQAs.