Anti-inflammatory Effects of Homotaurine in Patients With Amnestic Mild Cognitive Impairment
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 effica...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fnagi.2018.00285/full |
| _version_ | 1819099247562194944 |
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| author | Paola Bossù Francesca Salani Antonio Ciaramella Eleonora Sacchinelli Alessandra Mosca Alessandra Mosca Nerisa Banaj Francesca Assogna Francesca Assogna Maria Donata Orfei Carlo Caltagirone Carlo Caltagirone Walter Gianni Gianfranco Spalletta Gianfranco Spalletta |
| author_facet | Paola Bossù Francesca Salani Antonio Ciaramella Eleonora Sacchinelli Alessandra Mosca Alessandra Mosca Nerisa Banaj Francesca Assogna Francesca Assogna Maria Donata Orfei Carlo Caltagirone Carlo Caltagirone Walter Gianni Gianfranco Spalletta Gianfranco Spalletta |
| author_sort | Paola Bossù |
| collection | DOAJ |
| description | 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 apolipoprotein E (APOE) gene, the strongest genetic risk factor for AD. The serum levels of the pro-inflammatory mediators Interleukin (IL) 1β, Tumor necrosis factor-alpha (TNFα), IL-6 and IL-18, contextually with the anti-inflammatory molecules IL-18 binding protein (IL-18BP) and Transforming growth factor-beta (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. |
| first_indexed | 2024-12-22T00:43:51Z |
| format | Article |
| id | doaj.art-6a766362b80e445d9ab22ff7f6f249d6 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-22T00:43:51Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-6a766362b80e445d9ab22ff7f6f249d62022-12-21T18:44:36ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652018-11-011010.3389/fnagi.2018.00285288976Anti-inflammatory Effects of Homotaurine in Patients With Amnestic Mild Cognitive ImpairmentPaola Bossù0Francesca Salani1Antonio Ciaramella2Eleonora Sacchinelli3Alessandra Mosca4Alessandra Mosca5Nerisa Banaj6Francesca Assogna7Francesca Assogna8Maria Donata Orfei9Carlo Caltagirone10Carlo Caltagirone11Walter Gianni12Gianfranco Spalletta13Gianfranco Spalletta14Laboratory of Experimental Neuropsychobiology, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, ItalyLaboratory of Experimental Neuropsychobiology, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, ItalyLaboratory of Experimental Neuropsychobiology, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, ItalyLaboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, ItalyLaboratory of Psychology and Pediatric Pharmacology, Department of Neuroscience, University of Florence, Florence, ItalyMolecular Neurology Unit, CeSI-MeT, Center for Excellence on Aging and Translational Medicine, G. d’Annunzio University Chieti-Pescara, Chieti, ItalyLaboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, ItalyLaboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, ItalyCentro Fermi-Museo Storico della Fisica e Centro Studi e Ricerche Enrico Ferm, Rome, ItalyLaboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, ItalyDepartment of Medicine of Systems, Tor Vergata University of Rome, Rome, ItalyClinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, ItalyII Clinica Medica, Sapienza University of Rome, Rome, ItalyLaboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, ItalyMenninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, United StatesAlzheimer’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 apolipoprotein E (APOE) gene, the strongest genetic risk factor for AD. The serum levels of the pro-inflammatory mediators Interleukin (IL) 1β, Tumor necrosis factor-alpha (TNFα), IL-6 and IL-18, contextually with the anti-inflammatory molecules IL-18 binding protein (IL-18BP) and Transforming growth factor-beta (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.https://www.frontiersin.org/article/10.3389/fnagi.2018.00285/fulltramiprosateamnesic MCIAlzheimerAPOEinflammationcytokines |
| spellingShingle | Paola Bossù Francesca Salani Antonio Ciaramella Eleonora Sacchinelli Alessandra Mosca Alessandra Mosca Nerisa Banaj Francesca Assogna Francesca Assogna Maria Donata Orfei Carlo Caltagirone Carlo Caltagirone Walter Gianni Gianfranco Spalletta Gianfranco Spalletta Anti-inflammatory Effects of Homotaurine in Patients With Amnestic Mild Cognitive Impairment Frontiers in Aging Neuroscience tramiprosate amnesic MCI Alzheimer APOE inflammation cytokines |
| title | Anti-inflammatory Effects of Homotaurine in Patients With Amnestic Mild Cognitive Impairment |
| title_full | Anti-inflammatory Effects of Homotaurine in Patients With Amnestic Mild Cognitive Impairment |
| title_fullStr | Anti-inflammatory Effects of Homotaurine in Patients With Amnestic Mild Cognitive Impairment |
| title_full_unstemmed | Anti-inflammatory Effects of Homotaurine in Patients With Amnestic Mild Cognitive Impairment |
| title_short | Anti-inflammatory Effects of Homotaurine in Patients With Amnestic Mild Cognitive Impairment |
| title_sort | anti inflammatory effects of homotaurine in patients with amnestic mild cognitive impairment |
| topic | tramiprosate amnesic MCI Alzheimer APOE inflammation cytokines |
| url | https://www.frontiersin.org/article/10.3389/fnagi.2018.00285/full |
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