The interrelationships of CSF sTREM2, AD pathology, minimal depressive symptoms, and cognition in non-demented adults.

Background: Microglial activation has been suggested to be involved in the pathogenesis of depression and Alzheimer's disease (AD). Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is a marker of microglial activation. The purpose of this study was to investigate the interrelationships of cerebrospinal fluid (CSF) sTREM2, AD pathology, as well as minimal depressive symptoms (MDSs), and cognition.

Methods: A total of 545 non-demented individuals from the Alzheimer's Disease Neuroimaging Initiative cohort were included in our study. The average age of the total population was 72.6 years and the percentage of females was 42.6%. Linear regression models were conducted to investigate the linear relationships of MDSs with CSF sTREM2, AD pathology, cognition, and brain structure. Mediation models and structural equation models (SEM) were conducted to examine whether CSF sTREM2 mediated the relationships of MDSs with AD pathology and cognition.

Results: Results revealed that individuals with MDSs had lower CSF sTREM2 levels than normal controls. Linear regression showed that MDSs were linearly associated with CSF sTREM2 (P_FDR = 0.012) and amyloid biomarkers (P_FDR < 0.05), as well as cognitive scores (P_FDR < 0.05) and hippocampal volume (P_FDR = 0.003). Mediation analyses revealed that CSF sTREM2 mediated the association between MDSs and amyloid pathology, with the mediating proportions ranging from 6.030 to 18.894%. However, SEM failed to reveal that MDS affected cognition through CSF amyloid pathology and CSF sTREM2.

Conclusions: MDSs are associated with amyloid pathology and cognition. CSF sTREM2 may potentially be an intervenable target between depression and AD pathology.