TNF and Alzheimer disease: Unfortunately, the use of thalidomide in animal disease models and humans has proved difficult to translates as an approach to reduce neuroinflammation accompanying neurodegeneration [42] consequent to the development of intolerable off-target actions that proved dose-limiting prior to clinically relevant TNF-α lowering anti-inflammatory effects, as evidenced in a recent human Alzheimer’s disease thalidomide clinical trial [43].