One of the major histopathological hallmarks of Alzheimer's disease (AD) is 
cerebral deposits of extracellular β-amyloid peptides. Preclinical studies have 
pointed to glucagon-like peptide 1 (GLP-1) receptors as a potential novel target 
in the treatment of AD. GLP-1 receptor agonists, including exendin-4 and 
liraglutide, have been shown to promote plaque-lowering and mnemonic effects of 
in a number of experimental models of AD. Transgenic mouse models carrying 
genetic mutations of amyloid protein precursor (APP) and presenilin-1 (PS1) are 
commonly used to assess the pharmacodynamics of potential amyloidosis-lowering 
and pro-cognitive compounds. In this study, effects of long-term liraglutide 
treatment were therefore determined in two double APP/PS1 transgenic mouse 
models of Alzheimer's disease carrying different clinical APP/PS1 mutations, 
i.e. the 'London' (hAPPLon/PS1A246E) and 'Swedish' mutation variant 
(hAPPSwe/PS1ΔE9) of APP, with co-expression of distinct PS1 variants. 
Liraglutide was administered in 5 month-old hAPPLon/PS1A246E mice for 3 months 
(100 or 500 ng/kg/day, s.c.), or 7 month-old hAPPSwe/PS1ΔE9 mice for 5 months 
(500 ng/kg/day, s.c.). In both models, regional plaque load was quantified 
throughout the brain using stereological methods. Vehicle-dosed hAPPSwe/PS1ΔE9 
mice exhibited considerably higher cerebral plaque load than hAPPLon/PS1A246E 
control mice. Compared to vehicle-dosed transgenic controls, liraglutide 
treatment had no effect on the plaque levels in hAPPLon/PS1A246E and 
hAPPSwe/PS1ΔE9 mice. In conclusion, long-term liraglutide treatment exhibited no 
effect on cerebral plaque load in two transgenic mouse models of low- and 
high-grade amyloidosis, which suggests differential sensitivity to long-term 
liraglutide treatment in various transgenic mouse models mimicking distinct 
pathological hallmarks of AD.