APC and early-onset autosomal dominant Alzheimer disease: Extensive basic studies and preclinical injury studies of APC’s cytoprotective PAR1-biased signaling [4] have shown that signaling-selective APC mutants, e.g., 3K3A-APC lacking anticoagulant activity but retaining normal cytoprotective signaling, provide beneficial effects for sepsis, pneumonia, ischemia reperfusion injury in brain, heart and kidney, ocular inflammation, experimental autoimmune encephalitis, Alzheimer’s disease, amyotrophic lateral sclerosis, colitis, skin pathologies, and white matter stroke [2,3,25,26,27,28,29,30,31].