BACKGROUND:: In Alzheimer's disease (AD), microglia are activated by amyloid-beta (Aβ) to release IL6 among other cytokines, which in turn may be neurotoxic. Prior studies suggest that the brain inflammatory response to various antigens can be modeled by measuring the release of IL6 from peripheral blood mononuclear cells stimulated by lipopolysaccharide (LPS). We sought to replicate these results and extend to an AD-specific stimulus (Aβ).
METHOD:: PBMCs were purified from 5 AD and 5 age-gender matched cognitively healthy controls and exposed to LPS at two concentrations (20 and 100 ng/ml) and Aβ1-42(20 ug/ml). IL6 release was measured with standard ELISA kits, and the ratio of “IL6 release” with and without LPS stimulation was reported as the “IL6 release ratio.” Correlations were performed with Pearson's r2.
RESULTS:: IL6 release ratios were increased in AD participants as compared to cognitively normal age-gender matched controls with LPS 100 ng/ml exposure at a trend level (p=.07). Aβ1-42 increased the IL6 release ratio at a trend level (P=.07) with LPS 20 ng/ml exposure. IL6 release ratio was significantly correlated with worse performance on a verbal category fluency test (p=.03, r2=.49)and higher scores on the Neuropsychiatric Inventory (p=.01, r2=.63). There were trend level correlations of Il6 release with worse ratings on the CDR and MMSE.
CONCLUSIONS:: The IL6 release ratio derived from peripheral blood has potential as a biomarker of AD disease severity, both for cognitive outcomes and neuropsychiatric symptoms of AD.