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 β 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 Aβ42 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. ANN NEUROL 2024;96:61–73