TNFRSF1B and Alzheimer disease: Despite these drawbacks and the poor penetration of the blood-brain barrier by these agents, clinical trials with etanercept, a genetically engineered Fc fusion protein generated from the extracellular domain of human TNFR2 which blocks both sTNF and mTNF, have been conducted in patients with Alzheimer disease (AD), with significant cognitive and behavioral improvements [133, 134].