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Inverse association of cortisol serum levels with T-tau, P-tau 181 and P-tau 231 peptide levels and T-tau/Aβ 1–42 ratios in CSF in patients with mild Alzheimer’s disease dementia

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Abstract

Hypercortisolemia and increased levels of hyperphosphorylated tau proteins in cerebrospinal fluid (CSF) are common features with pathogenic relevance in Alzheimer`s disease (AD). Experimental studies point to an influence of cortisol on Aβ and tau pathology in AD. Association of both parameters have not yet been described in a sample of AD patients. In the present study, serum levels of cortisol were determined in 26 patients with mild AD dementia and 20 age-matched healthy elderly controls by ELISA. In addition, we measured in AD patients CSF levels of cortisol, total tau (T-tau), tau phosphorylated at threonine 181 (P-tau 181), tau protein phosphorylated at threonine 231 (P-tau 231) and beta-Amyloid (Aβ) 1–42 and determined T-tau/Aβ 1–42 ratios in CSF. We found in AD patients significantly increased cortisol serum levels (551.4 ± 146.1 nmol/l; P = 0.002) as compared to healthy controls (435.3 ± 83.9 nmol/l). In AD patients, cortisol serum levels were significantly inversely correlated with T-tau (r = −0.496; P = 0.01), P-tau 181 (r = −0.558; P = 0.003) and P-tau 231 (−0.500; P = 0.009) protein levels and T-tau/Aβ 1–42 ratios (r = −0.450; P = 0.021) in CSF. In addition, cortisol serum levels showed a trend of positive correlation with Aβ 1–42 CSF levels (r = 0.386; P = 0.052). However, no significant correlations of cortisol serum with CSF levels as well as cortisol CSF levels with CSF biomarkers could be detected in AD patients. In conclusion, our results show that increased cortisol serum but not CSF levels are associated with minor signs of AD pathology in CSF, indicating a putative neuroprotective effect of moderately elevated cortisol serum levels in patients with mild AD dementia.

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Acknowledgments

We thank AstraZeneca for measurement of P-tau 181 and P-tau 231 in CSF.

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Authors and Affiliations

  1. Dept. of Psychiatry and Psychotherapy, University of Tuebingen, Osianderstr. 24, 72076, Tuebingen, Germany

    Christoph Laske (Dr.), Elke Stransky, Gerhard W. Eschweiler & Thomas Leyhe

  2. Geriatric Center at the University Hospital of Tuebingen, Tuebingen, Germany

    Gerhard W. Eschweiler & Thomas Leyhe

  3. Dept. of Internal Medicine, Endocrinology, University of Tuebingen, Tuebingen, Germany

    Andreas Fritsche

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  1. Christoph Laske
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  2. Elke Stransky
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  4. Gerhard W. Eschweiler
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Correspondence to Christoph Laske.

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Laske, C., Stransky, E., Fritsche, A. et al. Inverse association of cortisol serum levels with T-tau, P-tau 181 and P-tau 231 peptide levels and T-tau/Aβ 1–42 ratios in CSF in patients with mild Alzheimer’s disease dementia. Eur Arch Psychiatry Clin Neurosci 259, 80–85 (2009). https://doi.org/10.1007/s00406-008-0838-3

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