Association of Cerebrospinal Fluid S100B Protein with Core Biomarkers and Cognitive Deficits in Prodromal and Mild Alzheimer’s Disease

BACKGROUND: Increased expression of the astroglial Ca2+-binding protein S100B has been observed in various neurodegenerative diseases and also seems to play a role in the unfolding of pathophysiological events at early stages of Alzheimer's disease (AD). OBJECTIVE: To examine the association of cerebrospinal fluid (CSF) levels of S100B with 1) established CSF core biomarkers total tau (tau), hyperphosphorylated tau (p-tau), and amyloid β1-42 (Aβ1-42) as well as neuron-specific enolase (NSE) CSF levels and 2) cognition in early AD and mild cognitive impairment (MCI) due to AD (MCI-AD). METHODS: Retrospective study assessing 49 pooled charts of Memory Clinic and inpatients diagnosed with AD (N = 26) and MCI-AD (N = 23) according to the National Institute of Aging and Alzheimer's Disease Association (NIA-AA) criteria. Neuropsychological testing was performed with the Consortium to Establish a Registry for AD (CERAD)-Plus battery. RESULTS: CSF levels of S100B correlated with NSE, but not the other CSF parameters. Stepwise multiple linear regression, adjusted for age, sex, and educational level, revealed that only increased CSF S100B was independently associated with lower CERAD-Plus total and Mini-Mental Status Examination scores together with poorer performance in wordlist learning (delayed recall and overall performance). We found no independent associations with other CSF biomarkers or cognitive domains. CONCLUSION: Our data suggest that CSF S100B may have a diagnostic value particularly at early stages of AD reflecting the significance of neuroinflammatory/astroglial processes. Thus, CSF S100B may complement the established array of available AD biomarkers to improve early stage diagnosis.