Attenuation of neurodegenerative phenotypes in Alzheimer-like presenilin 1/presenilin 2 conditional double knockout mice by EUK1001, a promising derivative of xanomeline

► Xanomeline has proven therapeutic effect in Alzheimer's disease patients, but caused so many adverse effects that its development was stopped. ► EUK1001, a fluorinated derivative of xanomeline, has greater affinity for M1 mAChRs and significantly less side effects than xanomeline. ► We explored the effects of EUK1001 and xanomeline in AD-like presenilin 1/presenilin 2 conditional double knockout (PS cDKO) mice. ► EUK1001 improved recognition memory deficits, ameliorated brain atrophy, and suppressed elevation of brain tau phosphorylation in PS cDKO mice. ► EUK1001 had advantages over xanomeline in most therapeutically relevant effects in PS cDKO mice.