FNDC5 and early-onset autosomal dominant Alzheimer disease: Finally, the effect of lean mass on Alzheimer’s disease and cognitive performance could also be mediated by new mechanisms, including by muscle secretion of circulating centrally acting myokines.45 46 Potentially relevant secreted myokines include irisin, brain derived neurotrophic factor 5, and cathepsin B. Identification of the key causal pathways might lead to development of treatments that harness and potentiate the neuroprotective effects of lean mass.