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). Here, PHF1 is linked to Brain atrophy.