Association of plasma irisin levels with amyloid burden in the Alzheimer's disease spectrum

Abstract INTRODUCTION This study investigated the association between plasma myokines, including irisin, and cerebral amyloid burden across the Alzheimer's disease (AD) continuum. METHODS A total of 100 participants were classified into four groups: amyloid‐negative cognitively unimpaired (A− CU), amyloid‐positive CU (A+ CU), A+ mild cognitive impairment (MCI), and A+ dementia of the Alzheimer's disease type (DAT). All participants underwent neuropsychological testing, brain magnetic resonance imaging, amyloid positron emission tomography, and plasma myokine assessment. Multivariable linear regression and mediation analyses were performed adjusting for covariates. RESULTS Irisin levels were significantly lower in all AD continuum groups compared to A– CU participants ( p < 0.001), while brain‐derived neurotrophic factor (BDNF) and fibroblast growth factor 21 (FGF21) showed no group differences. Higher irisin levels were associated with lower amyloid burden ( r = −0.24, p = 0.019). Mediation analysis demonstrated that amyloid burden mediated the relationship between irisin and cognitive outcomes, whereas no such effects were observed for BDNF or FGF21. DISCUSSION Irisin may play a key role in the muscle–brain axis by linking amyloid pathology to cognitive decline in AD.