SERUM S100B MEDIATES DEPRESSION’S EFFECT ON COGNITION

Abstract

The latent variable “δ” (for “dementia”) appears to be uniquely responsible for the dementing aspects of cognitive impairment. Age, depression, and the apolipoprotein E (APOE) e4 allele are independently associated with δ. S100b is a calcium- binding protein that is secreted mainly by astrocytes. S100b has been identified as a biomarker for mood/ depressive disorders. In addition, Brain level of S100b is altered in response to chronic use of anti-depressants. In this analysis, we combine SEM (Structural Equation Model) with longitudinal data from the Texas Alzheimer's Research and Care Consortium (TARCC) to explore whether S100b is a mediator of depression's specific effect on δ. We employed structural equation models (SEM) to examine the mediation effect of S100b on depression's association with δ in a well characterized cohort (TARCC). Subjects included n= 3385 TARCC participants [1240 cases of Alzheimer's Disease (AD), 688 “Mild Cognitive Impairment “(MCI) cases, and 1384 normal controls (NC)]. Serum S100b levels were determined at baseline by Luminex assay (Rules Based Medicine /Austin, TX). All observed measures were adjusted for education, ethnicity, gender, Geriatric Depression Scale (GDS) scores, Hb1Ac, apoE4 and HCY. S100b was additionally adjusted for batch effects. We used an ethnicity equivalent δ homolog (i.e., “dEQ”). Wave 2 dEQ scores were used. Thus, the model is longitudinal and arguable causal. Furthermore, we randomly divided the cohort into 2 groups. Group A (n = 1691) was used to construct the model, while Group B (n=1694) was used to replicate and verify the parameters of interest. Analyses were conducted in Analysis of Moment Structures (AMOS). Model fit was excellent [c2 = 519.912(49), p =0.0; CFI = 0.89; RMSEA = 0.053]. Serum S100b was found to mediate 18.3% of depression's association with Wave 2 dEQ scores (p<0.001). The effect generalized across random subsets of TARCC's sample. S100B plays a role in mediating depression's independent effects on dementia severity. High levels of serum S100B are dementing. S100B is a possible serum biomarker of depression in the elderly. S100B is a target for rational anti-dementia intervention, and may be amenable to modulation by SSRI.