Evidence for reduced anti-inflammatory microglial phagocytic response in late-life major depression

Area of Science:

• Neuroscience
• Immunology
• Psychiatry

Background:

• Major depressive disorder (MDD) is associated with Alzheimer's disease (AD), but the underlying mechanisms remain unclear.
• Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) is elevated in early AD stages.
• The behavior of CSF sTREM2 in individuals with MDD is not well understood.

Purpose of the Study:

• To investigate CSF sTREM2 levels in late-life major depression (LLMD) and compare them to healthy controls.
• To explore the relationship between CSF sTREM2, pro-inflammatory/anti-inflammatory markers, and AD biomarkers in LLMD and control groups.
• To test the hypothesis that CSF sTREM2 is elevated in MDD, similar to early AD.

Main Methods:

• A longitudinal study measuring CSF sTREM2 levels in 27 elderly individuals with LLMD and 19 healthy controls.
• Comparison of baseline CSF sTREM2 levels between LLMD and control groups.
• Assessment of changes in CSF sTREM2 levels at a 3-year follow-up, correlating with depression severity.

Main Results:

• CSF sTREM2 levels were significantly reduced in LLMD subjects compared to controls at baseline.
• This reduction in CSF sTREM2 was not significant at the 3-year follow-up, coinciding with improved depression severity.
• CSF sTREM2 correlated with AD biomarkers and pro-inflammatory cytokines in controls, but not in the LLMD group.

Conclusions:

• Contrary to the hypothesis, CSF sTREM2 levels are reduced in individuals with LLMD.
• The association between sTREM2, inflammation, and AD pathology differs between MDD and healthy controls.
• Impaired microglia phagocytic response to AD pathology may represent a novel mechanistic link between MDD and AD.