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Front. Aging Neurosci. | doi: 10.3389/fnagi.2018.00285

Anti-inflammatory effects of homotaurine in patients with amnestic mild cognitive impairment

  • 1Clinical and Behavioral Neurology, Fondazione Santa Lucia (IRCCS), Italy
  • 2Clinical and Behavior Neurology, Fondazione Santa Lucia (IRCCS), Italy
  • 3Neuroscience, Università degli Studi di Firenze, Italy
  • 4CeSI-MeT, Università degli Studi G. d'Annunzio Chieti e Pescara, Italy
  • 5Museo Storico della Fisica e Centro Studi e Ricerche "Enrico Fermi", Centro Fermi, Italy
  • 6Medicine of Systems, Università degli Studi di Roma Tor Vergata, Italy
  • 7II Clinica Medica, Università degli Studi di Roma La Sapienza, Italy
  • 8Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, United States

Alzheimer’s disease (AD) is a fatal dementing neurodegenerative disease, currently lacking an efficacious disease-modifying therapy. In the last years, there has been some interest in the use of homotaurine as a potential therapeutic compound for AD, but more work is still needed to prove its efficacy as disease modifier in dementia. Since inflammation is believed to play a key role in AD development, we sought to investigate here the in vivo homotaurine effect on inflammatory response in patients at the earliest stages of AD, i.e. suffering from amnestic mild cognitive impairment (aMCI). Thus, the present study aims to evaluate the effects of homotaurine supplementation on cytokine serum levels and memory performances in MCI patients.
Neuropsychological, clinical, and cytokine assessment was performed at baseline (T0) and after 1 year (T12) of homotaurine supplementation in 20 patients categorized as carriers (n=9) or no carriers (n=11) of the ε4 allele of the APOE gene, the strongest genetic risk factor for AD. The serum levels of the pro-inflammatory mediators IL-1β, TNFα, IL-6 and IL-18, contextually with the anti-inflammatory molecules IL-18 binding protein (IL-18BP) and TGFβ, were analyzed to explore significant differences in the inflammatory status between T0 and T12 in the two APOE variant carrier groups.
No significant differences over time were observed in patients as for most cytokines, except for IL-18. Following homotaurine supplementation, patients carrying the APOEε4 allele showed a significant decrease in IL-18 (both in its total and IL-18BP unbound forms), in turn associated with improved short-term episodic memory performance as measured by the recency effect of the Rey 15-word list learning test immediate recall.
Thus, homotaurine supplementation in individuals with aMCI may have a positive consequence on episodic memory loss due, at least in part, to homotaurine anti-inflammatory effects. This study strongly suggests that future research should focus on exploring the mechanisms by which homotaurine controls brain inflammation during AD progression.

Keywords: 3-Amino-1-propanesulfonic acid, tramiprosate, Amnesic MCI, Alzheimer Disease, APOE E4 allele, Inflammation, Cytokines, Interleukin-18

Received: 23 Jun 2017; Accepted: 30 Aug 2018.

Edited by:

Thomas Wisniewski, School of Medicine, New York University, United States

Reviewed by:

Luigia Trabace, University of Foggia, Italy
Elizabeth J. Johnson, Tufts University, United States  

Copyright: © 2018 Bossù, Salani, Palladino, Sacchinelli, Mosca, Banaj, Assogna, Orfei, Caltagirone, Gianni and Spalletta. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Paola Bossù, PHD., Fondazione Santa Lucia (IRCCS), Clinical and Behavioral Neurology, Via Ardeatina 306, Via Ardeatina 306, Rome, 00179, -- select state --, Italy, p.bossu@hsantalucia.it
Dr. Gianfranco Spalletta, MD, PHD., Fondazione Santa Lucia (IRCCS), Clinical and Behavior Neurology, Via Ardeatina 306, Via Ardeatina 306, Rome, 00179, -- select state --, Italy, g.spalletta@hsantalucia.it