TNF and early-onset autosomal dominant Alzheimer disease: Inhibition of RIPK1 by either genetic or pharmacological means in animal models is highly effective in blocking TNF-induced sepsis, including attenuation of hypothermia and complete rescue of lethality.65,66 Multiple RIPK1 inhibitors have been advanced beyond Phase I safety studies in human clinical trials for the treatment of human inflammatory and neurodegenerative diseases, including rheumatoid arthritis, psoriasis, inflammatory bowel disease, Alzheimer’s disease and amyotrophic lateral sclerosis.14