Lipopolysaccharide-Binding Protein, Soluble CD14, and the Long-Term Risk of Alzheimer's Disease: A Nested Case-Control Pilot Study of Older Community Dwellers from the Three-City Cohort.

Abstract

BACKGROUND:

Identifying the mechanisms involved in the pathogenesis of Alzheimer's disease (AD) remains crucially important. Chronic age-related low-grade inflammation is considered to be one such mechanism, although its causes are unclear. Lipopolysaccharide (LPS)-type endotoxins, a major component of the outer membrane of Gram-negative bacteria, are known as potent pro-inflammatory molecules. Therefore, we hypothesized that greater exposure to circulating LPS, potentially mediated by the inflammatory pathway, would be a key step of the onset of AD.

OBJECTIVE:

The aim of this study was to investigate the link between plasma endotoxin-exposure, inflammation, and AD.

METHODS:

Applying a nested case-control design, we evaluated the associations among baseline plasma endotoxin-exposure (assessed by measuring LPS-binding protein (LBP) and soluble cluster of differentiation-14 (sCD14) levels), inflammation (assessed by measuring interleukin-6 (IL6) levels), and the odds of developing AD over 12 years. Selected from a population-based cohort, 212 incident cases of AD were matched with 424 controls without dementia with regard to age, gender, and education level.

RESULTS:

After adjusting for a large set of confounders, including the use of anti-inflammatory drugs, only higher LBP levels were significantly associated with a 30% higher odds of developing AD over 12 years (OR 1.30, 95% CIs [1.07-1.59]), regardless of IL6 levels.

CONCLUSION:

This large case-control study provides preliminary results concerning plasma endotoxin-exposure among the elderly and suggests that higher LBP levels, an acute-phase reactant involved in the pro-inflammatory response to LPS, are associated with higher odds of developing AD.

• Authors: Perrine André, Cécilia Samieri, Charline Buisson, Jean-François Dartigues, Catherine Helmer, Fabienne Laugerette, Catherine Féart
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 71 Issue 3 Pg. 751-761 ( 2019) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 31450497 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acute-Phase Proteins
• Carrier Proteins
• IL6 protein, human
• Interleukin-6
• Lipopolysaccharide Receptors
• Membrane Glycoproteins
• lipopolysaccharide-binding protein

Topics

• Acute-Phase Proteins (genetics)
• Aged
• Aged, 80 and over
• Alzheimer Disease (epidemiology, genetics)
• Carrier Proteins (blood, genetics)
• Case-Control Studies
• Female
• France (epidemiology)
• Humans
• Incidence
• Independent Living
• Interleukin-6 (blood)
• Lipopolysaccharide Receptors (blood, genetics)
• Male
• Membrane Glycoproteins (blood, genetics)
• Pilot Projects
• Urban Population