Association between enlarged perivascular spaces and cerebrospinal fluid aquaporin-4 and tau levels: report from a memory clinic

Frontiers in Aging Neuroscience

Neuroscience

Giorgio Giulio Fumagalli¹  Federica Sorrentino²  Chiara Fenoglio²  Caterina Visconte²  Daniela Galimberti³  Luca Sacchi³  Manuela Pintus⁴  Giorgio Conte⁵  Fabio Triulzi⁵  Anna Margherita Pietroboni⁶  Maria Serpente⁶  Elio Scarpini⁶  Andrea Arighi⁶  Tiziana Carandini⁶  Marina Arcaro⁶  Valeria Elisa Contarino⁷ 

[1] Center for Mind/Brain Sciences (CIMeC), University of Trento, Rovereto, Italy;Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy;Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy;Neurodegenerative Diseases Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy;Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy;Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy;Neuroradiology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy;Neurodegenerative Diseases Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy;Neuroradiology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy;

关键词: glymphatic system;    aquaporin-4;    cerebrospinal fluid;    Alzheimer’s disease;    brain perivascular spaces;   

DOI  :  10.3389/fnagi.2023.1191714

 received in 2023-03-22, accepted in 2023-07-06,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Sacchi, Arcaro, Carandini, Pietroboni, Fumagalli, Fenoglio, Serpente, Sorrentino, Visconte, Pintus, Conte, Contarino, Scarpini, Triulzi, Galimberti and Arighi.