Table 1.

RAS medications in mouse models studies.

Drug	Class	Brain-Permeant	Mouse Model	Main Study Findings	Proposed Mechanisms	REFS
Perindopril	ACE Inhibitor	Yes	Aβ-injected mice; PS2APP mice	- Prevention of cognitive impairments - Reversion of cognitive deficits (working and recognition memory)	- Inhibition of brain ACE activities but not peripheral. - Reduction of microglia/astrocyte activation and oxidative stress	[55,56]
Captopril	ACE Inhibitor	Yes	Tg2576 mice; 5XFAD mice (and BV2 microglial cells)	- Chronic captopril slowed down the development of neurodegeneration signs	- Reduction of hippocampal ACE activity and ROS production - Reduction of IL-10 release by microglia - Decreased Aβ burden	[57,58]
Enalapril	Ace Inhibitor	No	Aβ-injected mice	- No effect on cognition - Very low inhibition of brain ACE activity	-	[55,56]
Imidapril	ACE Inhibitor	No	Aβ-injected mice	- No effect on cognition - Very low inhibition of brain ACE activity	-	[55,56]
Losartan	AT1R blocker	Yes	A/T mice; J20 APP mice	- losartan failed to restore spatial learning and memory in adult A/T mice but improved cerebrovascular activity - losartan ameliorated cognitive deficits in adult and aged J20 APP mice	- Attenuation of astrogliosis and normalization of AT1 and AT4 receptor levels (APP mice)	[59,60]
Valsartan	AT1R blocker	Yes	Tg2576 mice	- preventive valsartan administration attenuated cognitive dysfunction (improved spatial learning)	- Reduction of soluble extracellular oligomeric Aβ peptides in the brain	[61]
Telmisartan	AT1R blocker	Yes	Aβ-injected ddY mice; 5XFAD mice	- pretreatment with telmisartan prevented cognitive decline	- PPAR-γ activation and reduced Aβ deposition - Reduced activation of microglia and release of pro-inflammatory mediators and ROS	[62,63]
Olmesartan	AT1R blocker	No	APP23 mice; Aβ-Injected mice	- Attenuation of cerebrovascular dysfunction in APP23 mice; no reduction of brain Aβ levels - Improvement of cognitive functions in Aβ-Injected mice	- Decreased oxidative stress and neuroinflammation in the brain	[64]