Comparison of plasmatic interleukins patterns among cognitively unimpaired subjects, patients affected by mild cognitive impairment and subjects with Alzheimer's disease dementia

Background and aims We investigated a panel of plasma interleukins (ILs) levels hypothesized to play a role in aging and AD pathophysiology, in a pooled cohort of clinically characterized (according to NIA-AA core clinical criteria) cognitively unimpaired (HC), Mild Cognitive Impairment (MCI), and Alzheimer's Disease Dementia (ADD) individuals. Methods In 137 subjects (43HC, 63MCI and 31ADD), the plasma levels of IL1-b, IL-6, IL-10, IL-12, IL-6 receptor (IL-6R), TNF-a and TGF-b were measured by ELISA kits on samples collected at 8.00 AM and quickly frozen. Principal component analysis (PCA) was performed as the initial exploratory step; parametric statistic was assessed to evaluate group differences and association between IL and biological factors (age, sex, APOEe4). An exploratory clustering approach was carried out to investigate distinct biological profiles. Results In the total sample, IL12 was positively associated with age. We found a positive association between IL1β and IL12 and female sex and between IL12 and APOEe4 allele. MCI individuals, but not ADD patients, had higher concentrations of IL10 than HC. K-means clustering (k = 3) showed a cluster predominately characterized by ADD over the other two populations and lower IL12 and IL10 than the other two clusters. A component, mainly characterized by the IL-6R was negatively associated with MMSE. Conclusions Our preliminary results indicate a potential effect of critical biological factors such as aging, sex, and APOEe4 allele on some ILs hypothesized to be critical orchestrators of neuroinflammation. Speculative hypotheses based on translational data, are drawn upon the clusters found. Our results, support the investigation of IL-based profiles of neuroinflammation in AD.