Abstract: Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type III domain-containing protein 5 (FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective functions against Alzheimer’s disease, the most common form of dementia in the elderly, by improving cognitive function and reducing amyloid-β and tau pathologies as well as neuroinflammation in cell culture or animal models of Alzheimer’s disease. Although current and ongoing studies on irisin/FNDC5 show promising results, further mechanistic studies are required to clarify its potential as a meaningful therapeutic target for alleviating Alzheimer’s disease. We recently found that irisin treatment reduces amyloid-β pathology by increasing the activity/levels of amyloidβ-degrading enzyme neprilysin secreted from astrocytes. Herein, we present an overview of irisin/FNDC5’s protective roles and mechanisms against Alzheimer’s disease.

Key words: Alzheimer’s disease, exercise, fibronectin type III domain-containing protein 5 (FNDC5), irisin