APP Transgenic Mouse Study
Objective: Investigation of FPS-ZM1 effects on cognitive performance, cerebral blood flow, Aβ levels, and neuroinflammation in aged APP sw/0 transgenic mice
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Protocol Steps
In vitro cellular stress testing
FPS-ZM1 was tested for its ability to inhibit Aβ40- and Aβ42-induced cellular stress in RAGE-expressing cells in vitro
Note: Conducted in RAGE-expressing cells
View evidence from paper
“FPS-ZM1 blocked Aβ binding to the V domain of RAGE and inhibited Aβ40- and Aβ42-induced cellular stress in RAGE-expressing cells in vitro”
In vivo mouse brain studies
FPS-ZM1 was tested in the mouse brain in vivo to inhibit Aβ40- and Aβ42-induced cellular stress
Note: Conducted in aged APP sw/0 transgenic mice with established Aβ pathology
View evidence from paper
“FPS-ZM1 blocked Aβ binding to the V domain of RAGE and inhibited Aβ40- and Aβ42-induced cellular stress in the mouse brain in vivo”
Blood-brain barrier permeability assessment
FPS-ZM1 was assessed for its ability to cross the blood-brain barrier
Note: FPS-ZM1 demonstrated ability to readily cross the BBB
View evidence from paper
“FPS-ZM1 was nontoxic to mice and readily crossed the blood-brain barrier (BBB)”
RAGE-mediated Aβ influx inhibition
FPS-ZM1 was administered to aged APP sw/0 mice to inhibit RAGE-mediated influx of circulating Aβ40 and Aβ42 into the brain
Note: Conducted in aged APP sw/0 transgenic mice
View evidence from paper
“In aged APP sw/0 mice overexpressing human Aβ-precursor protein, FPS-ZM1 inhibited RAGE-mediated influx of circulating Aβ40 and Aβ42 into the brain”
Brain RAGE binding and β-secretase activity assessment
FPS-ZM1 binding to RAGE in brain was assessed, and its effects on β-secretase activity and Aβ production were measured
Note: FPS-ZM1 bound exclusively to RAGE in brain tissue
View evidence from paper
“In brain, FPS-ZM1 bound exclusively to RAGE, which inhibited β-secretase activity and Aβ production”
Microglia activation and neuroinflammation assessment
Effects of FPS-ZM1 on microglia activation and neuroinflammatory response were measured
Note: Conducted in aged APP sw/0 mice
View evidence from paper
“FPS-ZM1 suppressed microglia activation and the neuroinflammatory response”
Cognitive performance assessment
Cognitive performance was measured in aged APP sw/0 mice treated with FPS-ZM1
Note: Cognitive performance was normalized in treated mice
View evidence from paper
“Blockade of RAGE actions at the BBB and in the brain reduced Aβ40 and Aβ42 levels in brain markedly and normalized cognitive performance”
Cerebral blood flow assessment
Cerebral blood flow responses were measured in aged APP sw/0 mice treated with FPS-ZM1
Note: Cerebral blood flow responses were normalized in treated mice
View evidence from paper
“Blockade of RAGE actions at the BBB and in the brain normalized cerebral blood flow responses in aged APP sw/0 mice”
Brain Aβ level quantification
Aβ40 and Aβ42 levels in brain tissue were quantified following FPS-ZM1 treatment
Note: Aβ levels were markedly reduced in treated mice
View evidence from paper
“Blockade of RAGE actions at the BBB and in the brain reduced Aβ40 and Aβ42 levels in brain markedly”