HPX and early-onset autosomal dominant Alzheimer disease: Accumulation of the purine nucleobase hypoxanthine (Hpx) commonly associates with stress and disease such as hypoxia,31 colorectal cancer,32 dementia and Alzheimer’s disease,33 and multiple sclerosis.34 This Hpx accumulation indicates a stress-induced shift of decreased ATP production and regeneration, and/or increased ATP utilization, resulting in purine nucleotide degradation.27 Although Hpx increases during stress and disease, exogenous Hpx supply and accumulation promotes energy balance, wound healing, cytoskeletal capability, and tight junctional formation and function in vitro.