Work

Microglial activation: A process potentially related to Alzheimer's disease and late‐life major depression

Year: 2020

Type: article

Abstract: Background Since genetic findings have implicated microglia and TREM2 in the aetiology of neurodegenerative diseases, particularly Alzheimer's disease (AD), there have been numerous studies indicating changes in the levels of sTREM2 in cerebrospinal fluid (CSF) in sporadic and familial disease. Inflammation has also been implicated in depression and associated with an increased risk for AD. This prompted us to investigate levels of sTREM2 in late life major depression (LLMD). Method CSF was obtained from 47 older subjects with intact cognition having an MMSE score of at least 28 and no gross MRI abnormalities other than white matter hyperintensities (22 LLMD, 19 controls). Severity of depression was determined at baseline and screening visits using the HAM‐D. CSF sTREM2 was determined using an electrochemiluminescence immunoassay. We also determined AD biomarker levels and indices of blood brain barrier (BBB) dysfunction. Result sTREM2 levels were significantly lower in the CSF of LLMD subjects compared to controls (3476±525.1 pg/mL, 5178±2787 pg/mL p = 0.00351). Levels of sTREM2 were positively correlated with Aβ40 (r = 0.495, p = <0.001), Aβ42 (r = 0.461, p = 0.001) tTau (r = 0.417, p = 0.003) pTau181(r = 0.413, p = 0.004) and IL8 (r = 0.338, p = 0.022), this was driven by controls only. Markers of BBB integrity, the albumin quotient (AQ), cyclophilin A and soluble platelet derived growth factor beta (sPDGFβ) all show a positive correlation with sTREM2 (r = 0.503, p = 0.028; r = 0.479, p = 0.024; r = 0.455, p = 0.017 respectively) but this correlation is only seen in LLMD subjects, apart from sPDGFRβ, where a positive correlation was also seen in the whole cohort (r = 0.0337, p = 0.022). Conclusion The correlation of sTREM2 with indices of BBB dysfunction suggests that in LLMD the sTREM2 measured could be peripheral, and that there is a decrease or suppression of microglial activation. It is possible then, that LLMD leads to a higher risk of AD due to an inability of microglia to react appropriately and further studies should focus on investigating this in more detail.

Source: Alzheimer s & Dementia

DOI: 10.1002/alz.041950