Skip to main content

Advertisement

SpringerLink
Log in

Cerebrospinal Fluid Stanniocalcin-1 as a Biomarker for Alzheimer’s Disease and Other Neurodegenerative Disorders

  • Original Paper
  • Published:
NeuroMolecular Medicine Aims and scope Submit manuscript

Abstract

Stanniocalcin-1 (STC-1) is a nerve cell-enriched protein involved in intracellular calcium homeostasis regulation. Changes in calcium regulation are hypothesized to play a role in the pathophysiology of Alzheimer’s disease (AD). The expression of STC-1 increases in response to ischemic stroke, but whether it is altered in neurodegenerative disorder, particularly Alzheimer’s disease (AD), has not been investigated before. We measured STC-1 in cerebrospinal fluid (CSF) samples from a total of 163 individuals including AD, prodromal AD (pAD), mixed AD, stable mild cognitive impairment (sMCI), and diagnoses of other dementia than AD, as well as cognitively normal controls (CNC) enrolled at academic centers in France and Sweden. STC-1 concentration was reliably measureable in all CSF samples and was significantly increased in the initial exploratory cohort of neurochemically enriched AD patients versus AD biomarker-negative controls. In the second cohort, STC-1 was increased in AD versus pAD, and other dementia disorders, but the difference was not statistically significant. In the third cohort, there was no significant difference in STC-1 concentration between AD and CNC; however, STC-1 concentration was significantly decreased in patients with other dementia disorders compared with AD and CNC. Taken together, CSF STC-1 showed an increasing trend in AD, but the findings were not consistent across the three study cohorts. In contrast, CSF STC-1 concentrations were reduced in patients with dementia diagnoses other than AD, as compared with both AD patients and CNC. The findings from these studies suggest CSF STC-1 as a potential biomarker in differential diagnosis of dementias.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Blennow, K., de Leon, M. J., & Zetterberg, H. (2006). Alzheimer’s disease. Lancet, 368(9533), 387–403.

    Article  CAS  PubMed  Google Scholar 

  • Blennow, K., Hampel, H., Weiner, M., & Zetterberg, H. (2010). Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nature Reviews Neurology, 6(3), 131–144.

    Article  CAS  PubMed  Google Scholar 

  • Blennow, K., & Zetterberg, H. (2015). The past and the future of Alzheimer’s disease CSF biomarkers-a journey toward validated biochemical tests covering the whole spectrum of molecular events. Frontiers in Neuroscience, 9, 345.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bostrom, F., Hansson, O., Gerhardsson, L., Lundh, T., Minthon, L., Stomrud, E., et al. (2009). CSF Mg and Ca as diagnostic markers for dementia with lewy bodies. Neurobiology of Aging, 30(8), 1265–1271.

    Article  PubMed  Google Scholar 

  • Buerger, K., Ewers, M., Pirttila, T., Zinkowski, R., Alafuzoff, I., Teipel, S. J., et al. (2006). CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer’s disease. Brain a Journal of Neurology, 129(Pt 11), 3035–3041.

    Article  PubMed  Google Scholar 

  • Durukan Tolvanen, A., Westberg, J. A., Serlachius, M., Chang, A. C., Reddel, R. R., Andersson, L. C., et al. (2013). Stanniocalcin 1 is important for poststroke functionality, but dispensable for ischemic tolerance. Neuroscience, 229, 49–54.

    Article  CAS  PubMed  Google Scholar 

  • Ferri, C. P., Prince, M., Brayne, C., Brodaty, H., Fratiglioni, L., Ganguli, M., et al. (2005). Global prevalence of dementia: A Delphi consensus study. Lancet, 366(9503), 2112–2117.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hansson, O., Zetterberg, H., Buchhave, P., Londos, E., Blennow, K., & Minthon, L. (2006). Association between CSF biomarkers and incipient Alzheimer’s disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurology, 5(3), 228–234.

    Article  CAS  PubMed  Google Scholar 

  • Johansson, P., Mattsson, N., Hansson, O., Wallin, A., Johansson, J. O., Andreasson, U., et al. (2011). Cerebrospinal fluid biomarkers for Alzheimer’s disease: diagnostic performance in a homogeneous mono-center population. Journal of Alzheimer’s Disease JAD, 24(3), 537–546.

    PubMed  Google Scholar 

  • Khachaturian, Z. S. (1989). Calcium, membranes, aging, and Alzheimer’s disease. Introduction and overview. Annals of the New York Academy of Sciences, 568, 1–4.

    Article  CAS  PubMed  Google Scholar 

  • Khachaturian, Z. S. (1994). Calcium hypothesis of Alzheimer’s disease and brain aging. Annals of the New York Academy of Sciences, 747, 1–11.

    Article  CAS  PubMed  Google Scholar 

  • Lindsberg, P. J., Roine, R. O., Tatlisumak, T., Sairanen, T., & Kaste, M. (2000). The future of stroke treatment. Neurologic Clinics, 18(2), 495–510.

    Article  CAS  PubMed  Google Scholar 

  • Masters, C. L., Simms, G., Weinman, N. A., Multhaup, G., McDonald, B. L., & Beyreuther, K. (1985). Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proceedings of the National Academy of Sciences of the United States of America, 82(12), 4245–4249.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Olsson, B., Lautner, R., Andreasson, U., Ohrfelt, A., Portelius, E., Bjerke, M., et al. (2016). CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: A systematic review and meta-analysis. Lancet Neurology, 15(7), 673–684.

    Article  CAS  PubMed  Google Scholar 

  • Reitz, C., Tang, M. X., Schupf, N., Manly, J. J., Mayeux, R., & Luchsinger, J. A. (2010). Association of higher levels of high-density lipoprotein cholesterol in elderly individuals and lower risk of late-onset Alzheimer disease. Archives of Neurology, 67(12), 1491–1497.

    Article  PubMed  PubMed Central  Google Scholar 

  • Serlachius, M., Zhang, K. Z., & Andersson, L. C. (2004). Stanniocalcin in terminally differentiated mammalian cells. Peptides, 25(10), 1657–1662.

    Article  CAS  PubMed  Google Scholar 

  • Sparks, D. L., Scheff, S. W., Hunsaker, J. C., 3rd, Liu, H., Landers, T., & Gross, D. R. (1994). Induction of Alzheimer-like beta-amyloid immunoreactivity in the brains of rabbits with dietary cholesterol. Experimental Neurology, 126(1), 88–94.

    Article  CAS  PubMed  Google Scholar 

  • Subhash, M. N., Padmashree, T. S., Srinivas, K. N., Subbakrishna, D. K., & Shankar, S. K. (1991). Calcium and phosphorus levels in serum and CSF in dementia. Neurobiology of Aging, 12(4), 267–269.

    Article  CAS  PubMed  Google Scholar 

  • Wagner, G. F., Hampong, M., Park, C. M., & Copp, D. H. (1986). Purification, characterization, and bioassay of teleocalcin, a glycoprotein from salmon corpuscles of Stannius. General and Comparative Endocrinology, 63(3), 481–491.

    Article  CAS  PubMed  Google Scholar 

  • Yeung, B. H., Law, A. Y., & Wong, C. K. (2012). Evolution and roles of stanniocalcin. Molecular and Cellular Endocrinology, 349(2), 272–280.

    Article  CAS  PubMed  Google Scholar 

  • Yoshiko, Y., & Aubin, J. E. (2004). Stanniocalcin 1 as a pleiotropic factor in mammals. Peptides, 25(10), 1663–1669.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, K., Lindsberg, P. J., Tatlisumak, T., Kaste, M., Olsen, H. S., & Andersson, L. C. (2000). Stanniocalcin: A molecular guard of neurons during cerebral ischemia. Proceedings of the National Academy of Sciences of the United States of America, 97(7), 3637–3642.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, K. Z., Westberg, J. A., Paetau, A., von Boguslawsky, K., Lindsberg, P., Erlander, M., et al. (1998). High expression of stanniocalcin in differentiated brain neurons. The American Journal of Pathology, 153(2), 439–445.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The study was supported by grants from the Swedish Research Council, the European Research Council, Frimurarestiftelsen, the Knut and Alice Wallenberg Foundation, Alzheimerfonden, Hjärnfonden, the Torsten Söderberg Foundation, and Swedish State Support for Clinical Research. HH is supported by the AXA Research Fund, the Fondation Université Pierre et Marie Curie and the “Fondation pour la Recherche sur Alzheimer,” Paris, France. The research leading to these results has received funding from the program “Investissements d’avenir” ANR-10-IAIHU-06 (Agence Nationale de la Recherche-10-IA Agence Institut Hospitalo-Universitaire-6).

Author information

Authors and Affiliations

  1. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal Hospital, 43180, Mölndal, Sweden

    Pashtun Shahim, Kaj Blennow & Henrik Zetterberg

  2. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden

    Pashtun Shahim, Kaj Blennow & Henrik Zetterberg

  3. Department of Neuropsychiatry, Skaraborg Hospital, Falköping, Sweden

    Per Johansson

  4. Institute of Medicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

    Per Johansson & Johan Svensson

  5. Department of Endocrinology, Skaraborg Hospital, 541 85, Skövde, Sweden

    Johan Svensson

  6. AXA Research Fund & UPMC Chair, Paris, France

    Simone Lista & Harald Hampel

  7. IHU-A-ICM-Paris Institute of Translational Neurosciences, Pitié-Salpêtrière University Hospital, Paris, France

    Simone Lista

  8. Sorbonne Universities, Pierre and Marie Curie University, Paris 06, Institute of Memory and Alzheimer’s Disease (IM2A) & Brain and Spine Institute (ICM) UMR S 1127, Department of Neurology, Pitié-Salpêtrière University Hospital, Paris, France

    Harald Hampel

  9. Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland

    Leif Christer Andersson

  10. Department of Molecular Neuroscience, UCL Institute of Neurology, London, WC1N1PJ, UK

    Henrik Zetterberg

Authors
  1. Pashtun Shahim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kaj Blennow
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Per Johansson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Johan Svensson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Simone Lista
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Harald Hampel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Leif Christer Andersson
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Henrik Zetterberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pashtun Shahim.

Ethics declarations

Conflict of Interest

PS and JS report no conflict of interest. KB and HZ are co-founders of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg. KB has served as a consultant or ad advisory Boards for Eli Lilly, IBL International, Roche Diagnostics, Fujirebio Europe, and Novartis.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shahim, P., Blennow, K., Johansson, P. et al. Cerebrospinal Fluid Stanniocalcin-1 as a Biomarker for Alzheimer’s Disease and Other Neurodegenerative Disorders. Neuromol Med 19, 154–160 (2017). https://doi.org/10.1007/s12017-016-8439-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12017-016-8439-1

Keywords

Search

Navigation