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

Autor: Luca Sacchi, Marina Arcaro, Tiziana Carandini, Anna Margherita Pietroboni, Giorgio Giulio Fumagalli, Chiara Fenoglio, Maria Serpente, Federica Sorrentino, Caterina Visconte, Manuela Pintus, Giorgio Conte, Valeria Elisa Contarino, Elio Scarpini, Fabio Triulzi, Daniela Galimberti, Andrea Arighi
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Frontiers in Aging Neuroscience, Vol 15 (2023)
Druh dokumentu: article
ISSN: 1663-4365
DOI: 10.3389/fnagi.2023.1191714
Popis: 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.
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