Interplay between oxidative stress, neuroinflammatory cytokines and melatonin in Alzheimer's disease: Insights from cerebrospinal fluid analysis
1. Abstract: Background: Among neurodegenerative disorders Alzheimer's disease (AD) displays the highest prevalence and the projected increase in its incidence will require new advances in early diagnosis and treatment, particularly for distinguishing AD from other dementias. While beta-amyloi...
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Elsevier
2025-01-01
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| author | Francisco Artime-Naveda David Hevia Rebeca Alonso-Arias Carmen Martínez Isabel Quirós-González Rafael Cernuda-Cernuda Alejando Alvarez-Artime Iván Menéndez-Valle Rosa M. Sainz Juan C. Mayo |
| author_facet | Francisco Artime-Naveda David Hevia Rebeca Alonso-Arias Carmen Martínez Isabel Quirós-González Rafael Cernuda-Cernuda Alejando Alvarez-Artime Iván Menéndez-Valle Rosa M. Sainz Juan C. Mayo |
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| description | 1. Abstract: Background: Among neurodegenerative disorders Alzheimer's disease (AD) displays the highest prevalence and the projected increase in its incidence will require new advances in early diagnosis and treatment, particularly for distinguishing AD from other dementias. While beta-amyloid (Aβ) and tau biomarkers are currently used to discriminate AD from other tauopathies and dementias, additional indicators could enhance patient stratification for specific dementia types. The present study was designed to find potential associations among the classic neurologic markers, Aβ, total and phospho-tau (T-tau and P-tau), with other biomarkers including melatonin and its oxidative-derived metabolite, Formyl-N-acetyl-5-methoxykynurenamine (AFMK) levels, assayed in patients' cerebrospinal fluid (CSF) taken previously for diagnostic purposes. Other factors previously associated with the aetiology of AD, including redox indicators or proinflammatory biomarkers, were also included. Methods: The cross-sectional study included a cohort of 148 patients showing signs of dementia. A group of age-matched patients without neurological disorders were used as controls. CSF levels of Aβ, T-tau and P-tau were assayed, and patients were further classified according to threshold CSF levels of the three markers protein following the criteria of NIA-AA. Results: Correlational and group analysis showed a positive association between oxidative stress and neuronal damage. TNF-α negatively correlated with CSF Aβ levels (amyloid plaques) while only RANTES/CCL5 correlated positively with T-tau and P-tau. Qualitative analysis of the proinflammatory cytokines assayed showed a higher detection level in Aβ-positive patients. Regarding melatonin in the CSF, indolamine levels did not correlate with its major oxidative-derived metabolite, i.e., AFMK. However, melatonin CSF levels were significantly reduced in AD patients but not in OT. On the contrary, AFMK showed the opposite pattern, with higher levels in samples from patients displaying high T-tau and P-tau levels. Neuroinflammation was associated with Aβ deposits (low concentration in CSF), while oxidative stress significantly correlated with high T-tau and P-tau levels. Finally, among all the parameters assayed in CSF samples from the cohort studied, P-tau, in combination with antioxidant capacity, offered the best ROC curve for the diagnostic capacity to discriminate between AD and OT, showing an 85 % specificity. Conclusion: While oxidative stress is instead associated with high T- and P-tau levels, higher neuroinflammatory cytokines correlate with low CSF Aβ levels. An intriguing lack of correlation between neuroinflammation and melatonin found in this study could be as a result of sample size and requires further studies with a larger sample size. Even though indolamine levels in CSF drop significantly in AD, they do not correlate with AFMK, suggesting a different kynurenine synthesis source. None of them appear to discriminate between AD and OT. Finally, among all the parameters assayed in this study, P-tau in combination with antioxidant capacity, offered the best ROC curve for the diagnostic ability capacity to discriminate between AD and OT, showing an 85 % specificity. This study holds the potential to significantly improve patient stratification and contribute to the early diagnosis and treatment of Alzheimer's disease. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-bba2cb4007c04d618cb91dc75335c8cb2025-02-02T05:28:21ZengElsevierHeliyon2405-84402025-01-01112e41841Interplay between oxidative stress, neuroinflammatory cytokines and melatonin in Alzheimer's disease: Insights from cerebrospinal fluid analysisFrancisco Artime-Naveda0David Hevia1Rebeca Alonso-Arias2Carmen Martínez3Isabel Quirós-González4Rafael Cernuda-Cernuda5Alejando Alvarez-Artime6Iván Menéndez-Valle7Rosa M. Sainz8Juan C. Mayo9Departamento de Morfología y Biología Celular, School of Medicine, University of Oviedo, Julián Clavería 6, 33006, Oviedo, Spain; Instituto Universitario de Oncología del Principado de Asturias (IUOPA), 33006, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Avda. Hospital Universitario, 33011, Oviedo, SpainDepartamento de Morfología y Biología Celular, School of Medicine, University of Oviedo, Julián Clavería 6, 33006, Oviedo, Spain; Instituto Universitario de Oncología del Principado de Asturias (IUOPA), 33006, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Avda. Hospital Universitario, 33011, Oviedo, SpainInstituto Universitario de Oncología del Principado de Asturias (IUOPA), 33006, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Avda. Hospital Universitario, 33011, Oviedo, Spain; Department of Immunology, Central University Hospital of Asturias (HUCA), Oviedo, SpainInstituto de Investigación Sanitaria del Principado de Asturias (ISPA), Avda. Hospital Universitario, 33011, Oviedo, Spain; Department of Neurology, Central University Hospital of Asturias (HUCA), Oviedo, SpainDepartamento de Morfología y Biología Celular, School of Medicine, University of Oviedo, Julián Clavería 6, 33006, Oviedo, Spain; Instituto Universitario de Oncología del Principado de Asturias (IUOPA), 33006, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Avda. Hospital Universitario, 33011, Oviedo, SpainDepartamento de Morfología y Biología Celular, School of Medicine, University of Oviedo, Julián Clavería 6, 33006, Oviedo, Spain; Instituto Universitario de Oncología del Principado de Asturias (IUOPA), 33006, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Avda. Hospital Universitario, 33011, Oviedo, SpainDepartamento de Morfología y Biología Celular, School of Medicine, University of Oviedo, Julián Clavería 6, 33006, Oviedo, Spain; Instituto Universitario de Oncología del Principado de Asturias (IUOPA), 33006, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Avda. Hospital Universitario, 33011, Oviedo, SpainInstituto de Investigación Sanitaria del Principado de Asturias (ISPA), Avda. Hospital Universitario, 33011, Oviedo, Spain; Department of Neurology, Central University Hospital of Asturias (HUCA), Oviedo, SpainDepartamento de Morfología y Biología Celular, School of Medicine, University of Oviedo, Julián Clavería 6, 33006, Oviedo, Spain; Instituto Universitario de Oncología del Principado de Asturias (IUOPA), 33006, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Avda. Hospital Universitario, 33011, Oviedo, SpainDepartamento de Morfología y Biología Celular, School of Medicine, University of Oviedo, Julián Clavería 6, 33006, Oviedo, Spain; Instituto Universitario de Oncología del Principado de Asturias (IUOPA), 33006, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Avda. Hospital Universitario, 33011, Oviedo, Spain; Corresponding author. Departamento de Morfología y Biología Celular, School of Medicine, University of Oviedo, Julián Clavería 6, 33006, Oviedo, Spain.1. Abstract: Background: Among neurodegenerative disorders Alzheimer's disease (AD) displays the highest prevalence and the projected increase in its incidence will require new advances in early diagnosis and treatment, particularly for distinguishing AD from other dementias. While beta-amyloid (Aβ) and tau biomarkers are currently used to discriminate AD from other tauopathies and dementias, additional indicators could enhance patient stratification for specific dementia types. The present study was designed to find potential associations among the classic neurologic markers, Aβ, total and phospho-tau (T-tau and P-tau), with other biomarkers including melatonin and its oxidative-derived metabolite, Formyl-N-acetyl-5-methoxykynurenamine (AFMK) levels, assayed in patients' cerebrospinal fluid (CSF) taken previously for diagnostic purposes. Other factors previously associated with the aetiology of AD, including redox indicators or proinflammatory biomarkers, were also included. Methods: The cross-sectional study included a cohort of 148 patients showing signs of dementia. A group of age-matched patients without neurological disorders were used as controls. CSF levels of Aβ, T-tau and P-tau were assayed, and patients were further classified according to threshold CSF levels of the three markers protein following the criteria of NIA-AA. Results: Correlational and group analysis showed a positive association between oxidative stress and neuronal damage. TNF-α negatively correlated with CSF Aβ levels (amyloid plaques) while only RANTES/CCL5 correlated positively with T-tau and P-tau. Qualitative analysis of the proinflammatory cytokines assayed showed a higher detection level in Aβ-positive patients. Regarding melatonin in the CSF, indolamine levels did not correlate with its major oxidative-derived metabolite, i.e., AFMK. However, melatonin CSF levels were significantly reduced in AD patients but not in OT. On the contrary, AFMK showed the opposite pattern, with higher levels in samples from patients displaying high T-tau and P-tau levels. Neuroinflammation was associated with Aβ deposits (low concentration in CSF), while oxidative stress significantly correlated with high T-tau and P-tau levels. Finally, among all the parameters assayed in CSF samples from the cohort studied, P-tau, in combination with antioxidant capacity, offered the best ROC curve for the diagnostic capacity to discriminate between AD and OT, showing an 85 % specificity. Conclusion: While oxidative stress is instead associated with high T- and P-tau levels, higher neuroinflammatory cytokines correlate with low CSF Aβ levels. An intriguing lack of correlation between neuroinflammation and melatonin found in this study could be as a result of sample size and requires further studies with a larger sample size. Even though indolamine levels in CSF drop significantly in AD, they do not correlate with AFMK, suggesting a different kynurenine synthesis source. None of them appear to discriminate between AD and OT. Finally, among all the parameters assayed in this study, P-tau in combination with antioxidant capacity, offered the best ROC curve for the diagnostic ability capacity to discriminate between AD and OT, showing an 85 % specificity. This study holds the potential to significantly improve patient stratification and contribute to the early diagnosis and treatment of Alzheimer's disease.http://www.sciencedirect.com/science/article/pii/S240584402500221X |
| spellingShingle | Francisco Artime-Naveda David Hevia Rebeca Alonso-Arias Carmen Martínez Isabel Quirós-González Rafael Cernuda-Cernuda Alejando Alvarez-Artime Iván Menéndez-Valle Rosa M. Sainz Juan C. Mayo Interplay between oxidative stress, neuroinflammatory cytokines and melatonin in Alzheimer's disease: Insights from cerebrospinal fluid analysis Heliyon |
| title | Interplay between oxidative stress, neuroinflammatory cytokines and melatonin in Alzheimer's disease: Insights from cerebrospinal fluid analysis |
| title_full | Interplay between oxidative stress, neuroinflammatory cytokines and melatonin in Alzheimer's disease: Insights from cerebrospinal fluid analysis |
| title_fullStr | Interplay between oxidative stress, neuroinflammatory cytokines and melatonin in Alzheimer's disease: Insights from cerebrospinal fluid analysis |
| title_full_unstemmed | Interplay between oxidative stress, neuroinflammatory cytokines and melatonin in Alzheimer's disease: Insights from cerebrospinal fluid analysis |
| title_short | Interplay between oxidative stress, neuroinflammatory cytokines and melatonin in Alzheimer's disease: Insights from cerebrospinal fluid analysis |
| title_sort | interplay between oxidative stress neuroinflammatory cytokines and melatonin in alzheimer s disease insights from cerebrospinal fluid analysis |
| url | http://www.sciencedirect.com/science/article/pii/S240584402500221X |
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