PLASMA ENDOTOXEMIA, INFLAMMATION AND LONG-TERM RISK OF ALZHEIMER’S DISEASE AMONG ELDERLY COMMUNITY-DWELLERS

The gut microbiota is considered to be the main reservoir for pro-inflammatory lipopolysaccharide (LPS)-type endotoxins, and its disruptions have been suspected to be involved in central nervous system disorders, such as Alzheimer's disease (AD). Beneficial to the host when LPS is maintained in the gastrointestinal tract, gut microbiota dysbiosis could lead to increased translocation of the LPS across the intestinal barriers to end up in the bloodstream. However, the role of plasma endotoxemia, which has been defined as the presence of LPS in the bloodstream, in the pathogenesis of AD has not been thoroughly elucidated to date. In a nested case-control study, we evaluated the association between baseline plasma endotoxemia, which was assessed by measuring LPS-Binding Protein (LBP) and soluble Cluster of Differentiation-14 (sCD14) levels, inflammation, which was assessed by Interleukin-6 (IL6) levels, and the odds of developing AD over 12 years. Selected from a population-based cohort, 212 AD incident cases were matched on age, gender and educational level to 424 controls without dementia. Adjusting for a large set of confounders, including anti-inflammatory drugs, higher LBP levels were significantly associated with 30% higher odds of developing AD over 12 years (OR 1.30 95%CI [1.07 - 1.59]), independent of the IL6 levels. No association was found between sCD14, the soluble part of the CD14 receptor, or IL6 and AD. This large case-control study on the association between plasma endotoxemia and AD among elderly community-dwellers provides further potential pathways to investigate for the understanding of AD mechanisms. These results warrant further investigation.