Neuroinflammation in Comorbid Depression in Alzheimer’s Disease: a pilot study using post-mortem brain tissue.

Comorbid depression and Alzheimer’s disease (AD) is associated with poorer prognosis than either condition alone. Neuroinflammation has been implicated in the pathogenesis and progression of both depression and AD, but much of the existing research has been based on peripheral blood immune markers. Relatively little is known about the neuroinflammatory environment when these conditions occur simultaneously and using immune measures directly in the brain tissue. This pilot study aimed to examine brain inflammatory marker changes in AD cases comparing those with and without comorbid depression.
Post-mortem brain tissue from AD cases with depression (n=23) and AD cases with no history of psychiatric illness (n=25) were analyzed for a range of inflammatory markers, including markers of microglial function (Iba1, P2RY12, CD64 and CD68 measured by immunohistochemistry); endothelial inflammatory markers (ICAM-1 and VCAM-1 measured by ELISA); and cytokine levels (IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and TNF-α measured using Mesoscale Discovery Multiplex Assays).
Brains of AD cases with comorbid depression, compared with AD alone, had increased IL-4 in the superior frontal gyrus and increased TNFα & IL-12p70 in the insula. Levels of all other inflammatory markers including markers of microglial function and endothelial inflammation were similar between the two groups.
We found no consistent changes in cytokines between the two brain regions in individuals with comorbid depression in AD. Further work in larger cohorts is needed to understand brain region specificity of immune marker alterations and the relationship of these changes with pre-mortem clinical outcomes.