Association between lipopolysaccharide, immune biomarkers and cerebral amyloid‐beta deposition in older adults with mild cognitive impairment & major depressive disorder
Vivian Feng, Krista L. Lanctôt, Nathan Herrmann, Alex Kiss, Corinne E. Fischer, Alastair Flint, Linda Mah, Benoit H. Mulsant, Bruce G. Pollock, Tarek K. Rajji, Shankar Tumati, Nicolaas Paul L.G. Verhoeff, Ariel Graff‐Guerrero, Damien Gallagher- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
Inflammatory activation and increased immune response to lipopolysaccharide (LPS, a cell wall component of gut bacteria) is observed in both depression and cognitive decline. Depression is associated with accelerated cognitive decline, and persistent inflammatory activation may link depression and cognitive decline in later life. We determined if LPS is associated with inflammatory activation and cerebral deposition of amyloid‐beta (Abeta) in older adults with Mild Cognitive Impairment (MCI) and/or remitted Major Depressive Disorder (rMDD).
Method
Serum samples of LPS, LPS‐binding protein (LBP, which enhances the inflammatory response to LPS), and inflammatory markers (Interleukin 6 [Il‐6], C‐reactive protein [CRP], Monocyte Chemoattractant Protein 1 [MCP‐1]) were measured using ELISA. Abeta deposition was measured using PET neuroimaging using [11C]‐PIB radiotracer. Global amyloid burden was calculated using a composite Standardized Uptake Value Ratio (SUVR) score with the cerebellar cortex as the reference region. Multivariable linear regression analyses, adjusting for significant demographic and genetic variables, were conducted to determine if LPS, LBP, inflammatory biomarkers, MCI and rMDD were independently associated with global cerebral deposition of Abeta.
Result
Among 155 study participants (79 with MCI only, 54 with both MCI and rMDD, 22 with rMDD only) we found a median Abeta SUVR of 1.41 (IQR 0.57). There was no significant association between LPS (beta ‐1.28, 95% CI ‐11.69, 9.13, p = 0.8) or LBP (beta ‐0.02, 95% CI ‐0.05, 0.006, p = 0.12) and global deposition of Abeta, following adjustment for age, sex, and APOE genotype. LBP was positively correlated with inflammatory biomarkers: CRP (r = 0.49, p < 0.001) and IL‐6 (r = 0.21, p = 0.01) but no inflammatory biomarker was significantly associated with Abeta deposition. Having a history of rMDD (beta ‐0.09, 95% CI ‐0.26, 0.08, p = 0.28) or MCI alone (beta ‐0.11, 95% CI ‐0.47, 0.049, p = 0.11) was not associated with deposition of Abeta.
Conclusion
In this cross‐sectional analysis, we did not find an association between LPS/LBP, immune biomarkers, remitted MDD and global deposition of Abeta. Future analyses should examine the longitudinal relationships between peripheral and central biomarkers of immune activation with cerebral Abeta deposition in patients and controls.