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

Autor:	Sacchi L; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.; Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Arcaro M; Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Carandini T; Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Pietroboni AM; Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Fumagalli GG; Center for Mind/Brain Sciences (CIMeC), University of Trento, Rovereto, Italy., Fenoglio C; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy., Serpente M; Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Sorrentino F; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy., Visconte C; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy., Pintus M; Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy., Conte G; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.; Neuroradiology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Contarino VE; Neuroradiology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Scarpini E; Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Triulzi F; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.; Neuroradiology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Galimberti D; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.; Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Arighi A; Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in aging neuroscience [Front Aging Neurosci] 2023 Jul 20; Vol. 15, pp. 1191714. Date of Electronic Publication: 2023 Jul 20 (Print Publication: 2023).
DOI:	10.3389/fnagi.2023.1191714
Abstrakt:	Background: Perivascular 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. Methods: We 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. Results: Cerebrospinal 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). Conclusion: We provide evidence that CSO-EPVS and CSF-AQP4 might be clinically meaningful biomarkers of glymphatic dysfunction and associated neurodegeneration. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Sacchi, Arcaro, Carandini, Pietroboni, Fumagalli, Fenoglio, Serpente, Sorrentino, Visconte, Pintus, Conte, Contarino, Scarpini, Triulzi, Galimberti and Arighi.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu