Lipopolysaccharide, Immune Biomarkers and Cerebral Amyloid-Beta Deposition in Older Adults With Mild Cognitive Impairment & Major Depressive Disorder.

• What is the primary question addressed by this study? To determine whether lipopolysaccharide and inflammatory biomarkers are key drivers of cerebral amyloid-beta (Abeta) deposition in older adults with mild cognitive impairment (MCI) and remitted major depressive disorder (rMDD). • What is the main finding of this study? While many participants demonstrated high Abeta deposition we did not find significant associations between lipopolysaccharide, peripheral inflammatory biomarkers, remitted major depressive disorder, and cerebral deposition of Abeta. • What is the meaning of the finding? While this study did not demonstrate a significant cross sectional association it is possible that inflammatory activation may be associated with Abeta deposition earlier in the disease process and may be more relevant among those with chronic inflammatory activation and more persistent depression. Future longitudinal studies would help clarify whether these potentially modifiable risk factors play a role in the evolution of Alzheimer's neuropathology. Inflammatory activation and increased immune response to lipopolysaccharide occur in both depression and cognitive decline and may link these two conditions. We investigated whether lipopolysaccharide (LPS), LPS binding protein (LBP) and peripheral biomarkers of immune response were associated with increased cerebral deposition of amyloid-beta (Abeta) in older adults with mild cognitive impairment (MCI) and remitted major depressive disorder (rMDD). Cross-sectional analysis. Five academic health centers in Toronto. Older adults with MCI with/without rMDD. We investigated the associations among serum LPS, LBP, biomarkers of inflammatory activation – Interleukin-6 (IL-6), C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), and cerebral Abeta deposition quantified by positron emission tomography. Among 133 study participants (82 with MCI and 51 with MCI+rMDD) there was no association between LPS (beta – 0.17, p = 0.8) or LBP (beta - 0.11, p = 0.12) and global deposition of Abeta following adjustment for age, gender, and APOE genotype in multivariable regression analyses. LBP was positively correlated with CRP (r = 0.5, p <0.001) and IL-6 (r = 0.2, p = 0.02) but no inflammatory biomarker was associated with Abeta deposition; rMDD was not associated with deposition of Abeta (beta -0.09, p = 0.22). In this cross-sectional analysis, we did not find an association among LPS/LBP, immune biomarkers or rMDD and global deposition of Abeta. Future analyses should assess the longitudinal relationships between peripheral and central biomarkers of immune activation, depression and cerebral Abeta deposition. [ABSTRACT FROM AUTHOR]