2. Academic Validation
  3. Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation

Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation

  • Int J Mol Sci. 2017 Dec 19;18(12):2764. doi: 10.3390/ijms18122764.
Marcus O W Grimm 1 2 3,  Andrea Thiel 4,  Anna A Lauer 5,  Jakob Winkler 6,  Johannes Lehmann 7 8,  Liesa Regner 9,  Christopher Nelke 10,  Daniel Janitschke 11,  Céline Benoist 12,  Olga Streidenberger 13,  Hannah Stötzel 14,  Kristina Endres 15,  Christian Herr 16,  Christoph Beisswenger 17,  Heike S Grimm 18,  Robert Bals 19,  Frank Lammert 20,  Tobias Hartmann 21 22 23
Affiliations

Affiliations

  • 1 Experimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany. [email protected].
  • 2 Neurodegeneration and Neurobiology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany. [email protected].
  • 3 Deutsches Institut für DemenzPrävention (DIDP), Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany. [email protected].
  • 4 Experimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany. [email protected].
  • 5 Experimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany. [email protected].
  • 6 Experimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany. [email protected].
  • 7 Experimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany. [email protected].
  • 8 Department of Internal Medicine II-Gastroenterology, Saarland University Hospital, Saarland University, Kirrberger Str. 100, 66421 Homburg/Saar, Germany. [email protected].
  • 9 Experimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany. [email protected].
  • 10 Experimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany. [email protected].
  • 11 Experimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany. [email protected].
  • 12 Experimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany. [email protected].
  • 13 Experimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany. [email protected].
  • 14 Experimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany. [email protected].
  • 15 Department of Psychiatry and Psychotherapy, Clinical Research Group, University Medical Centre Johannes Gutenberg, University of Mainz, Untere Zahlbacher Str. 8, 55131 Mainz, Germany. [email protected].
  • 16 Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Kirrberger Str. 1, 66421 Homburg/Saar, Germany. [email protected].
  • 17 Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Kirrberger Str. 1, 66421 Homburg/Saar, Germany. [email protected].
  • 18 Experimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany. [email protected].
  • 19 Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Kirrberger Str. 1, 66421 Homburg/Saar, Germany. [email protected].
  • 20 Department of Internal Medicine II-Gastroenterology, Saarland University Hospital, Saarland University, Kirrberger Str. 100, 66421 Homburg/Saar, Germany. [email protected].
  • 21 Experimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany. [email protected].
  • 22 Neurodegeneration and Neurobiology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany. [email protected].
  • 23 Deutsches Institut für DemenzPrävention (DIDP), Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany. [email protected].
PMID: 29257109 DOI: 10.3390/ijms18122764
Abstract

Alzheimer's disease (AD) is characterized by extracellular plaques in the brain, mainly consisting of Amyloid-β (Aβ), as derived from sequential cleavage of the amyloid precursor protein. Epidemiological studies suggest a tight link between hypovitaminosis of the secosteroid vitamin D and AD. Besides decreased vitamin D level in AD patients, an effect of vitamin D on Aβ-homeostasis is discussed. However, the exact underlying mechanisms remain to be elucidated and nothing is known about the potential effect of vitamin D analogues. Here we systematically investigate the effect of vitamin D and therapeutically used analogues (maxacalcitol, calcipotriol, alfacalcidol, paricalcitol, doxercalciferol) on AD-relevant mechanisms. D₂ and D₃ analogues decreased Aβ-production and increased Aβ-degradation in neuroblastoma cells or vitamin D deficient mouse brains. Effects were mediated by affecting the Aβ-producing enzymes BACE1 and γ-secretase. A reduced secretase activity was accompanied by a decreased BACE1 protein level and nicastrin expression, an essential component of the γ-secretase. Vitamin D and analogues decreased β-secretase activity, not only in mouse brains with mild vitamin D hypovitaminosis, but also in non-deficient mouse brains. Our results further strengthen the link between AD and vitamin D, suggesting that supplementation of vitamin D or vitamin D analogues might have beneficial effects in AD prevention.

Keywords

Aβ-degradation; amyloid precursor protein; amyloid-β; secretases; vitamin D; vitamin D analogues.

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