Moreover, suppression of endogenous TWEAK using blocking antibodies ameliorated Fn14-dependent synaptic deficits in mouse models of stroke and Alzheimer's disease, indicating not only that the TWEAK-Fn14 pathway is an important synaptic organizer across multiple circuits in the brain but also that disruptions in TWEAK-Fn14 signaling may contribute to neurological dysfunction related to brain disorders. This evidence concerns the gene TNFSF12 and early-onset autosomal dominant Alzheimer disease.