Exercise hormone irisin is a critical regulator of cognitive function.

"rna-seq datasets are available at the gene expression omnibus (geo) repository under accession super serial number gse174212 which contains gse174210 gse174211 and gse179078 datasets."

"COMPETING INTERESTS STATEMENT: The authors declare the following competing interests: B.M.S and C.D.W. hold a patent related to irisin (WO2015051007A1). B.M.S. and C.D.W. are academic co-founders and consultants for Aevum Therapeutics. C.D.W. has a financial interest in Aevum Therapeutics, a company developing drugs which harness the protective molecular mechanisms of exercise to treat neurodegenerative and neuromuscular disorders. Dr. Wrann’s interests were reviewed and are managed by Massachusetts General Hospital and Mass General Brigham in accordance with their conflict of interest policies. The other authors declare no competing interests."

"This work was supported by NIH grant no. NS087096 (C.D.W), AG062904 (C.D.W), AG064580 (C.D.W), 1R01AR065538 (R.J.S), 1R01CA193520 (R.J.S), R01DK062472 (R.J.S), S10RR027931 (R.J.S), K01DK089145 (A.B.S), R01DK062472 (A.B.S), the Cure Alzheimer’s Fund (C.D.W, S.H. C., and R.E.T), an Alzheimer Association Research Grant (C.D.W), a SPARC Award from the McCance Center for Brain Health (C.D.W), the NeuroBehavior Laboratory Pilot Project Research Award from the Harvard NeuroDiscovery Center (C.D.W), the Hassenfeld Clinical Scholar Award (C.D.W), the Claflin Distinguished Scholar Award (C.D.W), the Harvard Brain Science Initiative Young Scientist Travel Award (M.R.I), the MSFHR (B.R.C. and L.E.B.B.), the FRAXA (B.R.C. and L.E.B.B.), the FXRFC (B.R.C. and L.E.B.B.), the NSERC (B.R.C. and L.E.B.B.), the CIHR (B.R.C. and L.E.B.B.), the JPB Foundation (B.M.S), and the MGH Molecular Imaging Core (R.J.S). We thank H. Van Praag for critical comments on the study design, data analysis, and the manuscript, and for providing us with the RV-CAG-GFP and RV-SYN-GTRgp. We acknowledge K. Gerber for technical assistance. We thank all members of the Wrann lab for helpful discussions. We thank Z. Herbert from the Molecular Biology Core Facilities at the Dana-Farber Cancer Institute for his support. We would like to acknowledge J. Long for help with designing the AAV8-irisin. We acknowledge the MGH Viral Vector Core (supported by NIH/NINDS P30NS04776) and the Penn Vector core for technical and instrument support. Schematic icons in Figures 4 and 5 were created with BioRender.com."