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Irisin is involved in various metabolic pathways and is suggested to be a potential agent capable of preventing onset of Alzheimer's disease (AD) and ameliorating AD neuropathology and cognitive deficits. In the present study, the serum levels of Irisin and Amyloid-β (Aβ) peptides and the neurocognitive performance among obese individuals at genetic risk for AD were investigated. The correlations between Irisin and AD-related neuropathological and neurocognitive indices were also explored. Thirty-two individuals with a family history o