Irisin Levels in Cerebrospinal Fluid Correlate with Biomarkers and Clinical Dementia Scores in Alzheimer Disease

Objective: Irisin, released by muscles during exercise, was recently identified as a neuroprotective factor in mouse models of Alzheimer disease (AD). In a cohort of AD patients, we studied cerebrospinal fluid (CSF) and plasma irisin levels, sex interactions, and correlations with disease biomarkers. Methods: Correlations between CSF and plasma irisin levels and AD biomarkers (amyloid beta 1-42, hyperphosphorylated tau, and total tau [t-tau]) and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) were analyzed in a cohort of patients with Alzheimer dementia (n = 82), mild cognitive impairment (n = 44), and subjective memory complaint (n = 20) biologically characterized according to the recent amyloid/tau/neurodegeneration classification. Results: CSF irisin was reduced in Alzheimer dementia patients (p < 0.0001), with lower levels in female patients. Moreover, CSF irisin correlated positively with A beta 42 in both female (r = 0.379, p < 0.001) and male (r = 0.262, p < 0.05) patients, and negatively with CDR-SOB (r = -0.234, p < 0.05) only in female patients. A negative trend was also observed between CSF irisin and t-tau levels in all patients (r = -0.144, p = 0.082) and in the female subgroup (r = -0.189, p = 0.084). Interpretation: The results highlight the relationship between irisin and biomarkers of AD pathology, especially in females. Our findings also offer perspectives toward the use of irisin as a marker of the AD continuum.