Association between enlarged perivascular spaces and cerebrospinal fluid aquaporin-4 and tau levels: report from a memory clinic
BackgroundPerivascular spaces (PVS) are fluid-filled compartments that dilate in response to many different conditions. A high burden of enlarged PVS (EPVS) in the centrum semiovale (CSO) has been linked to neurodegeneration. Moreover, an increase in cerebrospinal fluid (CSF) levels of aquaporin-4 (...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1191714/full |
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| author | Luca Sacchi Luca Sacchi Marina Arcaro Tiziana Carandini Anna Margherita Pietroboni Giorgio Giulio Fumagalli Chiara Fenoglio Maria Serpente Federica Sorrentino Caterina Visconte Manuela Pintus Giorgio Conte Giorgio Conte Valeria Elisa Contarino Elio Scarpini Fabio Triulzi Fabio Triulzi Daniela Galimberti Daniela Galimberti Andrea Arighi |
| author_facet | Luca Sacchi Luca Sacchi Marina Arcaro Tiziana Carandini Anna Margherita Pietroboni Giorgio Giulio Fumagalli Chiara Fenoglio Maria Serpente Federica Sorrentino Caterina Visconte Manuela Pintus Giorgio Conte Giorgio Conte Valeria Elisa Contarino Elio Scarpini Fabio Triulzi Fabio Triulzi Daniela Galimberti Daniela Galimberti Andrea Arighi |
| author_sort | Luca Sacchi |
| collection | DOAJ |
| description | BackgroundPerivascular spaces (PVS) are fluid-filled compartments that dilate in response to many different conditions. A high burden of enlarged PVS (EPVS) in the centrum semiovale (CSO) has been linked to neurodegeneration. Moreover, an increase in cerebrospinal fluid (CSF) levels of aquaporin-4 (AQP4), a water channel expressed on PVS-bounding astrocytes, has been described in patients with neurodegenerative dementia. Our aim was to investigate the relationship between neurodegenerative diseases and two putative glymphatic system biomarkers: AQP4 and EPVS.MethodsWe included 70 individuals, 54 patients with neurodegenerative diseases and 16 subjects with non-degenerative conditions. EPVS were visually quantified on MRI-scans applying Paradise’s scale. All subjects underwent lumbar puncture for the measurement of AQP4 levels in the cerebrospinal fluid (CSF). CSF levels of amyloid-β-1-42, phosphorylated and total tau (tTau) were also measured. Linear regression analyses were adjusted for age, sex, education and disease duration, after excluding outliers.ResultsCerebrospinal fluid (CSF)-AQP4 levels were independent predictors of total (β = 0.28, standard error [SE] = 0.08, p = 0.001), basal ganglia (β = 0.20, SE = 0.08, p = 0.009) and centrum semiovale EPVS (β = 0.37, SE = 0.12, p = 0.003). tTau levels predicted CSO-EPVS (β = 0.30, SE = 0.15, p = 0.046). Moreover, increased levels of AQP4 were strongly associated with higher levels of tTau in the CSF (β = 0.35, SE = 0.13, p = 0.008).ConclusionWe provide evidence that CSO-EPVS and CSF-AQP4 might be clinically meaningful biomarkers of glymphatic dysfunction and associated neurodegeneration. |
| first_indexed | 2024-03-12T22:45:43Z |
| format | Article |
| id | doaj.art-f72906f6021b41eca1e6417da00c6254 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-03-12T22:45:43Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-f72906f6021b41eca1e6417da00c62542023-07-21T06:26:08ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652023-07-011510.3389/fnagi.2023.11917141191714Association between enlarged perivascular spaces and cerebrospinal fluid aquaporin-4 and tau levels: report from a memory clinicLuca Sacchi0Luca Sacchi1Marina Arcaro2Tiziana Carandini3Anna Margherita Pietroboni4Giorgio Giulio Fumagalli5Chiara Fenoglio6Maria Serpente7Federica Sorrentino8Caterina Visconte9Manuela Pintus10Giorgio Conte11Giorgio Conte12Valeria Elisa Contarino13Elio Scarpini14Fabio Triulzi15Fabio Triulzi16Daniela Galimberti17Daniela Galimberti18Andrea Arighi19Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, ItalyNeurodegenerative Diseases Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyNeurodegenerative Diseases Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyNeurodegenerative Diseases Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyNeurodegenerative Diseases Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyCenter for Mind/Brain Sciences (CIMeC), University of Trento, Rovereto, ItalyDepartment of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, ItalyNeurodegenerative Diseases Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, ItalyDepartment of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, ItalyDepartment of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyDepartment of Pathophysiology and Transplantation, University of Milan, Milan, ItalyNeuroradiology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyNeuroradiology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyNeurodegenerative Diseases Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Pathophysiology and Transplantation, University of Milan, Milan, ItalyNeuroradiology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, ItalyNeurodegenerative Diseases Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyNeurodegenerative Diseases Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyBackgroundPerivascular spaces (PVS) are fluid-filled compartments that dilate in response to many different conditions. A high burden of enlarged PVS (EPVS) in the centrum semiovale (CSO) has been linked to neurodegeneration. Moreover, an increase in cerebrospinal fluid (CSF) levels of aquaporin-4 (AQP4), a water channel expressed on PVS-bounding astrocytes, has been described in patients with neurodegenerative dementia. Our aim was to investigate the relationship between neurodegenerative diseases and two putative glymphatic system biomarkers: AQP4 and EPVS.MethodsWe included 70 individuals, 54 patients with neurodegenerative diseases and 16 subjects with non-degenerative conditions. EPVS were visually quantified on MRI-scans applying Paradise’s scale. All subjects underwent lumbar puncture for the measurement of AQP4 levels in the cerebrospinal fluid (CSF). CSF levels of amyloid-β-1-42, phosphorylated and total tau (tTau) were also measured. Linear regression analyses were adjusted for age, sex, education and disease duration, after excluding outliers.ResultsCerebrospinal fluid (CSF)-AQP4 levels were independent predictors of total (β = 0.28, standard error [SE] = 0.08, p = 0.001), basal ganglia (β = 0.20, SE = 0.08, p = 0.009) and centrum semiovale EPVS (β = 0.37, SE = 0.12, p = 0.003). tTau levels predicted CSO-EPVS (β = 0.30, SE = 0.15, p = 0.046). Moreover, increased levels of AQP4 were strongly associated with higher levels of tTau in the CSF (β = 0.35, SE = 0.13, p = 0.008).ConclusionWe provide evidence that CSO-EPVS and CSF-AQP4 might be clinically meaningful biomarkers of glymphatic dysfunction and associated neurodegeneration.https://www.frontiersin.org/articles/10.3389/fnagi.2023.1191714/fullglymphatic systemaquaporin-4cerebrospinal fluidAlzheimer’s diseasebrain perivascular spaces |
| spellingShingle | Luca Sacchi Luca Sacchi Marina Arcaro Tiziana Carandini Anna Margherita Pietroboni Giorgio Giulio Fumagalli Chiara Fenoglio Maria Serpente Federica Sorrentino Caterina Visconte Manuela Pintus Giorgio Conte Giorgio Conte Valeria Elisa Contarino Elio Scarpini Fabio Triulzi Fabio Triulzi Daniela Galimberti Daniela Galimberti Andrea Arighi Association between enlarged perivascular spaces and cerebrospinal fluid aquaporin-4 and tau levels: report from a memory clinic Frontiers in Aging Neuroscience glymphatic system aquaporin-4 cerebrospinal fluid Alzheimer’s disease brain perivascular spaces |
| title | Association between enlarged perivascular spaces and cerebrospinal fluid aquaporin-4 and tau levels: report from a memory clinic |
| title_full | Association between enlarged perivascular spaces and cerebrospinal fluid aquaporin-4 and tau levels: report from a memory clinic |
| title_fullStr | Association between enlarged perivascular spaces and cerebrospinal fluid aquaporin-4 and tau levels: report from a memory clinic |
| title_full_unstemmed | Association between enlarged perivascular spaces and cerebrospinal fluid aquaporin-4 and tau levels: report from a memory clinic |
| title_short | Association between enlarged perivascular spaces and cerebrospinal fluid aquaporin-4 and tau levels: report from a memory clinic |
| title_sort | association between enlarged perivascular spaces and cerebrospinal fluid aquaporin 4 and tau levels report from a memory clinic |
| topic | glymphatic system aquaporin-4 cerebrospinal fluid Alzheimer’s disease brain perivascular spaces |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1191714/full |
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