SERUM S100B MEDIATES DEPRESSION’S EFFECT ON COGNITION

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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.