Alzheimer’s disease is characterized by neuroinflammation and neural accumulation of pathological tau. One candidate for treatment is a recently discovered hormone irisin, which is a cleaved product from the fibronectin type III domain-containing protein 5 (FNDC5) transmembrane protein. We have preliminary data showing that weekly injections of recombinant irisin decreased neuroinflammation and tau pathology in 4-month old female htau mice that express a mutant, humanized gene associated with late-onset Alzheimer’s disease. In the current study, we determined how changes in treatment frequency and age affected neuropathology, inflammation, and FNDC5 levels in htau mice and their wildtype littermates that lack any form of tau.