AUTHOR=Sacchi Luca , Arcaro Marina , Carandini Tiziana , Pietroboni Anna Margherita , Fumagalli Giorgio Giulio , Fenoglio Chiara , Serpente Maria , Sorrentino Federica , Visconte Caterina , Pintus Manuela , Conte Giorgio , Contarino Valeria Elisa , Scarpini Elio , Triulzi Fabio , Galimberti Daniela , Arighi Andrea 

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

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=15

YEAR=2023

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1191714

DOI=10.3389/fnagi.2023.1191714

ISSN=1663-4365

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>Cerebrospinal fluid (CSF)-AQP4 levels were independent predictors of total (β = 0.28, standard error [SE] = 0.08, <italic>p</italic> = 0.001), basal ganglia (β = 0.20, SE = 0.08, <italic>p</italic> = 0.009) and centrum semiovale EPVS (β = 0.37, SE = 0.12, <italic>p</italic> = 0.003). tTau levels predicted CSO-EPVS (β = 0.30, SE = 0.15, <italic>p</italic> = 0.046). Moreover, increased levels of AQP4 were strongly associated with higher levels of tTau in the CSF (β = 0.35, SE = 0.13, <italic>p</italic> = 0.008).</p></sec><sec><title>Conclusion</title><p>We provide evidence that CSO-EPVS and CSF-AQP4 might be clinically meaningful biomarkers of glymphatic dysfunction and associated neurodegeneration.</p></sec>