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Published on: November 27, 2019
Association of CSF sTREM2, a marker of microglia activation, with cholinergic basal forebrain volume in major
Stefan Teipel1, Davide Bruno2, Chelsea Reichert Plaska3
1Department of Psychosomatic Medicine, University Medicine Rostock, Rostock, Germany; DZNE, German Center for Neurodegenerative Diseases, Rostock, Germany.
Background:
Inflammatory mechanisms are believed to contribute to the manifestation of major depressive disorder (MDD). Central cholinergic activity may moderate this effect. Here, we tested if volume of the cholinergic basal forebrain is associated with cerebrospinal fluid (CSF) levels of sTREM2 as a marker of microglial activation in people with late life MDD.
Methods:
Basal forebrain volume was determined from structural MRI scans and levels of CSF sTREM2 with immunoassay in 29 people with late-life MDD and 20 healthy older controls at baseline and 3 years follow-up. Associations were determined using Bayesian analysis of covariance.
Results:
We found moderate level of evidence for an association of lower CSF levels of sTREM2 at 3 years follow up with MDD (Bayes factor in favor of an effect = 7.9). This level of evidence prevailed when controlling for overall antidepressant treatment and CSF levels of markers of AD pathology, i.e., Aβ42/Aβ40, ptau181 and total tau. Evidence was in favor of absence of an effect for baseline levels of CSF sTREM2 in MDD cases and for baseline and follow up data in controls.
Limitations:
The sample size of repeated CSF examinations was relatively small. Therefore, we used Bayesian sequential analysis to assess if effects were affected by sample size. Still, the number of cases was too small to stratify effects for different antidepressive treatments.
Conclusions:
Our data agree with the assumption that central cholinergic system integrity may contribute to regulation of microglia activity in late-life MDD.
Insights
In late-life major depressive disorder (MDD), lower cerebrospinal fluid (CSF) sTREM2 levels at follow-up were associated with the condition, suggesting cholinergic system integrity may regulate microglial activity.
Area of Science:
- Neuroscience
- Psychiatry
- Immunology
Background:
- Inflammation is implicated in major depressive disorder (MDD).
- Central cholinergic activity may modulate inflammatory effects in MDD.
- Microglial activation is a key inflammatory process in the brain.
Purpose of the Study:
- To investigate the association between cholinergic basal forebrain volume and cerebrospinal fluid (CSF) sTREM2 levels in late-life MDD.
- To explore sTREM2 as a marker of microglial activation in the context of MDD and cholinergic integrity.
- To examine these associations over a 3-year follow-up period.
Main Methods:
- Structural MRI was used to determine basal forebrain volume.
- CSF sTREM2 levels were measured using immunoassay.
- Bayesian analysis of covariance was employed to assess associations in 29 MDD patients and 20 controls.
Main Results:
- Moderate evidence supports an association between lower CSF sTREM2 levels at 3-year follow-up and MDD (Bayes factor = 7.9).
- This association remained significant after controlling for antidepressant treatment and Alzheimer's disease biomarkers.
- No significant associations were found for baseline CSF sTREM2 levels in MDD cases or in controls at baseline or follow-up.
Conclusions:
- Findings support the hypothesis that central cholinergic system integrity influences microglial activity regulation in late-life MDD.
- sTREM2 may serve as a relevant biomarker for microglial activation in this population.
- Further research with larger sample sizes is needed to explore treatment-specific effects.
