Table 2. Studies characterizing the effect of GLP-1 receptor agonists and other related compounds in different transgenic mouse models on β-amyloid plaque pathology.

Transgenic mouse model	Plaque onset in model	Drug	Dosage	Gender (n)	Treatment start (age)	Treatment duration	Effect on plaque load	Ref.
APPSwe/PS1ΔE9	4–6 mo	Exendin-4	25 nmol/kg/day, i.p.	Male (n = 6)	13–14 months	3 weeks	Reduced plaque load (cortex)	[21]
APPSwe/PS1ΔE9	4–6 mo	Sitagliptin Exendin-4	20 mg/kg/day, p.o. 2 pM/kg/min, s.c. osmotic minipump	Male (n = 6)	7 months	12 weeks	Reduced plaque load (sitagliptin, hippocampus) No effect (exendin-4, hippocampus)	[63]
APPSwe/PS1ΔE9	4–6 mo	GLP-1(9–36)amide	151 nmol/kg/day, s.c. osmotic minipump	Male (n = 7)	10–12 months	2 weeks	No effect (hippocampus)	[65]
APPSwe/PS1ΔE9	4–6 mo	Liraglutide	25 nmol/kg/day, i.p.	Male (n = 6)	7 months	8 weeks	Reduced plaque load (hippocampus, cortex)	[23]
APPSwe/PS1ΔE9	4–6 mo	Liraglutide	25 nmol/kg/day, i.p.	Female (n = 5)	7 months	8 weeks	Reduced plaque load (cortex)	[61]
APPSwe/PS1ΔE9	4–6 mo	Liraglutide	25 nmol/kg/day, i.p.	Male (n = 12)	14 months	8 weeks	Reduced plaque load (cortex)	[25]
APPSwe/PS1ΔE9	4–6 mo	Liraglutide Lixisenatide	2.5–25 nmol/kg/day, i.p.1-10 nmol/kg/day, i.p.	Male (n = 11–12)	7 months	10 weeks	Reduced plaque load (cortex)	[22]
APPSwe/PS1ΔE9	4–6 mo	Liraglutide	25 nmol/kg/day, i.p.	Male (n = 6)	8 weeks	8 months	Reduced plaque load (cortex)	[62]
APP/PS1-21	2–3 mo	Val8(GLP-1)	25 nmol/kg/day, i.p.	Male (n = 11–15)	9 and 18 months	3 weeks	No effect (cortex)	[64]
APPSwe/PS1M146V/TauP301L	6 mo	Exendin-4	3.5 pM/kg/min, s.c.osmotic minipump	Male (n = 3), Female (n = 4)	11–12.5 months	16 weeks	No effect (hippocampus, cortex)	[17]
APPSwe/PS1M146V/TauP301L	6 mo	Exendin-4	119 nmol/kg/day, i.p. (5 days a week)	Male/female (n = 5)	3 months	9 months	No effect (hippocampus)	[54]

The transgenic mouse models of Alzheimer’s disease display age-dependent differences in the onset of plaque aggregation, i.e. APP_Swe/PS1_ΔE9, 4–6 month of age [36, 46]; APP/PS1-21, 2–3 month of age [66]; APP_Swe/PS1_M146V/Tau_P301L, 6 months of age [67].