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

Brain Behav Immun

Geriatric Psychiatry Division, Nathan S Kline Institute for Psychiatric Research, Orangeburg, NY, USA; Department of Psychiatry and Pathology, New York University Grossman School of Medicine, New York, NY, USA. Electronic address:

Published: August 2024

Major depressive disorder (MDD) is associated with Alzheimer's disease (AD) but the precise mechanisms underlying this relationship are not understood. While it is well established that cerebrospinal fluid (CSF) soluble levels of triggering receptor expressed on myeloid cells 2 (sTREM2) increase during early stages of AD, how sTREM2 levels behave in subjects with MDD is not known. In a longitudinal study, we measured CSF sTREM2 levels in 27 elderly cognitively intact individuals with late-life major depression (LLMD) and in 19 healthy controls. We tested the hypothesis that, similarly to what happens in early stages of AD, CSF sTREM2 would be elevated in MDD. In addition, we compared the associations of CSF sTREM2, pro- and anti- inflammatory, and AD biomarkers in LLMD and control subjects. Surprisingly, we found that mean CSF sTREM2 levels were significantly reduced in LLMD compared to controls. This reduction was no longer significant at the 3-year follow-up visit when depression severity improved. In addition, we found that CSF sTREM2 was associated with AD biomarkers and proinflammatory cytokines in controls but not in LLMD. These findings suggest that impaired microglia phagocytic response to AD pathology may be a novel link between MDD and AD.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11270917PMC
http://dx.doi.org/10.1016/j.bbi.2024.05.030DOI Listing

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