Levels of astrocyte‐derived glial fibrillary acidic protein (GFAP) and S100 calcium‐binding protein B (S100B) in the cerebrospinal fluid within the early stages of Alzheimer´s Disease

Abstract

AbstractBackgroundThe quantitative analysis of biomarker proteins in the cerebrospinal fluid (CSF) substantiates the clinical diagnosis of Alzheimer´s disease (AD). A substantial problem in the early diagnosis of AD is that clinical symptoms as measured by neuropsychological tests appear only after massive cell loss has already occurred in the brain. However, when the disease manifests, abeta‐ and tau‐protein levels have already become static. In this study, we asked whether concentrations of the astrocyte‐derived proteins glial fibrillary acidic protein (GFAP) and S100 calcium‐binding protein B (S100B) in CSF might serve as markers of pathophysiological events and astrocyte reactivation in the course of AD. Although, there are some previously studies reporting high GFAP levels in cerebrospinal fluid of AD group, the CSF levels of GFAP and S100B in the early course of the AD have not been reported.MethodsWe measured the levels of GFAP and S100B in the CSF of healthy control subjects (n = 90), first degree relatives of AD (parent or sibling, n = 46), subjective memory decline (SCD) (n = 211), mild cognitive impairment (MCI) (n = 114) and AD (n = 65) patients in a well‐structured cohort (DELCODE Cohort), which has a larger sample size than previous studies.ResultsAfter comparing the CSF levels of GFAP in the study groups, we found that healthy controls had significantly lower GFAP levels than AD patients (p = 0.001, Figure 1) and the MCI patients (p = 0,004, Figure 1). It might prove to be a very important evidence of the role of astrogliosis in early stages. Furthermore, no significantly differences were found in levels of S100B, although S100B mean values show also gradual increasing from SCD to AD (Figure 2). As a note to the reader, we also found that there was low correlation between the levels of glial markers (GFAP und S100B) and markers of classical biomarkers (Aβ‐42, Ratio Aβ‐42/Aβ‐40, Total‐τ, Phospho‐τ‐181) of neurodegeneration in the disease course.ConclusionThis result may prove the role of early reactive astrocytes in early stages of disease. And this finding could lead to develop another treatment concepts targeting the early reactive astrocytes.