TNF and Alzheimer disease: Interestingly, ADAM17, an extracellular protease leading to soluble TNFα, the TNF receptor interactor TNIP1, and components of the linear ubiquitination machinery linear ubiquitination chain assembly complex (LUBAC): HOIL, SHARPIN, and the negative regulator OTULIN are all affected by mutations in AD patients (Figure 2, red boxes).