Since RIPK1 activation and necroptosis have been genetically and mechanistically linked with human neurodegenerative diseases such as MS [8, 9, 14], ALS [18] and Alzheimer’s disease (AD) [30, 31], keen interests have been sparkled on developing CNS-penetrant new RIPK1 inhibitors as drug candidates to treat CNS diseases [17]. Here, RIPK1 is linked to early-onset autosomal dominant Alzheimer disease.