[Effects of JAL-TA9 on cognitive deficits in Alzheimer's disease model mouse].

Many studies have been conducted to find an effective drug for Alzheimer's disease (AD) treatment. However, no effective drug applicable for clinical use has been developed. Recently, the FDA approved Lecanemab, an antibody drug that acts as an aggregation inhibitor against Amyloid-beta (Aβ), for AD treatment. However, there are still no fundamental drugs for AD. In this study, we present a strategy for AD treatment that removes Aβ by cleavage reaction using one of the Catalytides, JAL-TA9 (YKGSGFRMI). A single dose of JAL-TA9 administered into the CA1 region of the hippocampus and the intraventricular space improved the deficits in short-term memory of APP-knock-in mice. It also improved the memory of Aβ25-35-induced model mice, as evaluated by the Y-maze and objective recognition tests. These data strongly suggest that JAL-TA9 could be effective in treating AD. However, these administration methods are difficult to apply clinically due to their high invasiveness. Thus, we tested the improvement effects of dementia by administering JAL-TA9 nasally. It is very interesting and exciting that the dementia of Aβ25-35 induced AD model mice was improved by four applications once every three days. These results strongly suggest that JAL-TA9 is the best candidate for AD treatment because it is effective even in the late stage of AD.