CHF5074, a new microglial modulator, attenuates memory deficit in Alzheimer's 
disease transgenic mice. In this study, the effect of an acute or subacute 
CHF5074 treatment on in vivo novel object recognition test and on 
[³H]Acetylcholine (ACh) and GABA release in pre-plaque (7-month-old) Tg2576 mice 
have been compared with those induced by the γ-secretase inhibitor LY450139 
(semagacestat). Vehicle-treated Tg2576 mice displayed an impairment of 
recognition memory compared with wild-type animals. This impairment was 
recovered in transgenic animals acutely treated with CHF5074 (30 mg/kg), while 
LY450139 (1, 3, 10 mg/kg) was ineffective. In frontal cortex synaptosomes from 
vehicle-treated Tg2576 mice, K⁺-evoked [³H]ACh release was lower than that 
measured in wild-type mice. This reduction was absent in transgenic animals 
subacutely treated with CHF5074 (30 mg/kg daily for 8 days), while it was 
slightly, not significantly, amplified by LY450139 (3 mg/kg daily for 8 days). 
There were no differences between the groups on spontaneous [³H]ACh release as 
well as spontaneous and K⁺-evoked GABA release. These results suggest that 
CHF5074 has beneficial effects on visual memory and cortical cholinergic 
dysfunctions in pre-plaque Tg2576 mice. Together with previous findings, these 
data suggest that CHF5074 could be a possible candidate for early Alzheimer's 
disease therapeutic regimens.