Article
Levels of astrocyte-derived proteins increase in the cerebrospinal fluid of Alzheimer’s disease patients and inversely correlate to cognitive performance
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Authors
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Carola Schipke
- Charité University Medicine, Neuropathology, Berlin, Germany; Berlin Insitute of Health, BIH, Berlin, Germany
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Manuel Fuentes-Casan
- Charité University Medicine, Psychiatry and Psychotherapy, CBF, Berlin, Germany
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Herlin Megges
- Charité University Medicine, Psychiatry and Psychotherapy, CBF, Berlin, Germany
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Frank L. Heppner
- Charité University Medicine, Neuropathology, Berlin, Germany; Berlin Insitute of Health, BIH, Berlin, Germany
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Oliver Peters
- Charité University Medicine, Psychiatry and Psychotherapy, CBF, Berlin, Germany; Berlin Insitute of Health, BIH, Berlin, Germany
| Published: | August 25, 2015 |
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Outline
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Introduction: The quantitative analysis of biomarker proteins in the cerebrospinal fluid (CSF) substantiates the clinical diagnosis of Alzheimer’s disease (AD). But, when the disease becomes manifest in mental disturbances, Abeta and tau-protein levels have already become static and are therefore unsuitable to predict disease progression.
Objectives: We asked whether concentrations of the astrocyte-derived proteins glial fibrillary acidic protein (GFAP) and S100B in patients’ CSF might serve as markers of pathophysiological events in the course of AD.
We also used a transgenic mouse model exhibiting amyloid plaque formation (APP/PS1 transgenic mice) to ask whether in LTP experiments the amount of GFAP-positive astrocytes correlates to the level of LTP in aged mice.
Patients & methods: We used ELISA kits for the quantitative analysis of GFAP (IBL-International, Hamburg, Germany) and S100B (IBL) in CSF and compared mean levels between AD patients (n=36) and healthy control patients (n=35) and then correlated levels of astroglial proteins in the CSF and cognitive performance (MMST values).
In transgenic, aged (10-15 months) mice (n=10), we performed LTP experiments at the Schaffer collateral synapses in the CA1 region of the Hippocampus.
Results: We found that both GFAP and S100ß levels in CSF are significantly higher in the group of AD patients than in the control group. There is also a correlation between the S100B and GFAP levels and the patients’ cognitive performance as measured by the MMST values (r=-0,42 and r=-0,38). These correlations are within the range of correlations of the classical biomarkers to the MMST values (Abeta42-MMST r=0,63 ; t-Tau-MMST r=-0,49 in this cohort).
When correlating the number of astrocytes in the CA1 region to the level of LTP, 30 min after induction, we found a significant correlation of the number of astrocytes per mm3 to the level of LTP (r=0,648, p<0,05).
Conclusions: The astrocyte-derived proteins GFAP and S100B can be reliably detected in CSF and might serve as markers for pathophysiological events in the course of AD. Additional measurement of astroglial biomarkers might allow an improved pathobiological staging of AD, also since astrocytes appear to play a functional role in memory formation in the context of an AD-like pathology.
