TABLE 1.

Influence of stress/stress signaling.

	AD neuropathology	Neuroinflammation	Other
AD transgenic rodent models	Tg2576 + Isolation stress: ↑ plasma corticosterone ↑ GC receptor levels ↑ Ab plaque deposition (Dong et al., 2008). ↑Ab production ↓neurogenesis (hippocampus) (Dong et al., 2004). CRF overexpression AβPP + /CRF + /tTA + transgenic mice ↑ Aβ burden in the cortex and dendritic loss (Dong et al., 2012). CRFR1-KO-PSAPP Mice vs. PSAPP ↓ Aβ40, Aβ42 ↓ AβPP CTFs ↓ Insulin degrading enzyme (IDE): mechanism may involve Aβ production rather than clearance (Campbell et al., 2015a,b).	APP/hAβ/PS1 mice Intrinsic ↑ CRF PVN, hippocampus, amygdala (Guo et al., 2012). 11-month old 5x FAD Mice Intrinsic ↓ CB1r ↓MAGL ↑AGLL ↑ CB2r Hippocampus (Medina-Vera et al., 2020).	Tg2576 + Isolation stress: Impaired contextual memory (Dong et al., 2004). Tg2576 cognitive decline rescued with GC receptor antagonist RU486 (Lante et al., 2015).
Relevant exposures/modifications in non-AD tg rodents/cells	Chronic stress and excessive GC production: (middle aged rats) -APP processing shifts toward the amyloidogenic pathway (Catania et al., 2009). Repeated stress: ↑tPre-pathological Tau-p (Rissman et al., 2012). CRF-overexpressing mice: Brain atrophy at 3–6 months of age ↑ p- (GSK-3B) ↑ MAPK ↑ p38 ↑ ERK1/2. ↑ JNK-mediated tau-p at sites AT8, PHF-1 ↑tau aggregates (Campbell et al., 2015a,b). ↓CREB activation ↓ BDNF transport ↑BDNF transport velocity and distance traveled (Le et al., 2016).	Repeated stress: In mPFC, hippocampus: ↑ Dendritic atrophy ↓ glial counts ↓ proliferation (McEwen and Magarinos, 2001; Radley et al., 2004; Banasr and Duman, 2007; Banasr et al., 2007; Radley et al., 2008). Chronic unpredictable stress (CUS) ↓neurotrophins ↓ hippocampal neurogenesis ↓ dendritic arborization ↑arborization ↑arborization (Farooq et al., 2012; Campos et al., 2013b,2017)	CRF-overexpressing mice: -Brain atrophy (3–6 months) -Hippocampal dependent learning deficits (9 months) (Campbell et al., 2015a,b). Chronic unpredictable stress (CUS): ↑anxiety and depression-like behaviors ↓cognitive performance (Farooq et al., 2012; Campos et al., 2013b,2017)