Associations of circulating resistin with Alzheimer's disease biomarkers and cognitive function in the preclinical stage of Alzheimer's disease.

BackgroundResistin is a circulating protein linked to systemic metabolic disorders and inflammation, both of which can contribute to the pathogenesis of Alzheimer's disease (AD). However, the role of resistin during the preclinical stage of AD and its associations with amyloid-β and tau pathology have not been established.ObjectiveTo measure plasma resistin concentrations in cognitively normal older adults and examine its association with cerebrospinal fluid (CSF) AD biomarkers and neuropsychological measures.Methods155 (64 men and 91 women) cognitively normal (Clinical Dementia Rating 0) volunteers met all study criteria with 55 (29 men and 26 women) categorized as preclinical AD based on established CSF criteria. Plasma resistin concentrations were measured by immunoassay.ResultsSince plasma resistin concentrations were higher in men compared to women, all analyses were sex stratified. In men, plasma resistin concentrations were significantly higher in preclinical AD compared to biomarker negative controls and were associated with CSF concentrations of tau and p-tau181; however, after correcting for multiple comparisons, there were no significant associations with any AD biomarkers. Furthermore, plasma resistin concentrations were significantly associated with semantic fluency but not with episodic memory or executive function. In women, plasma resistin concentrations were similar between preclinical AD and controls, and there were no significant associations with CSF AD biomarkers and cognitive measures.ConclusionsThese findings raise the possibility that, in men, alterations in peripheral resistin signaling occur during the earliest stages of AD and could represent an early link between systemic metabolic and inflammation dysregulation in AD.