血管周围间隙增宽与脑脊液水通道蛋白-4及tau蛋白水平之间的关联：来自记忆门诊的报告
Association between enlarged perivascular spaces and cerebrospinal fluid aquaporin-4 and tau levels: report from a memory clinic.
作者信息
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
机构信息
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
出版信息
Front Aging Neurosci. 2023 Jul 20;15:1191714. doi: 10.3389/fnagi.2023.1191714. eCollection 2023.
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, = 0.001), basal ganglia (β = 0.20, SE = 0.08, = 0.009) and centrum semiovale EPVS (β = 0.37, SE = 0.12, = 0.003). tTau levels predicted CSO-EPVS (β = 0.30, SE = 0.15, = 0.046). Moreover, increased levels of AQP4 were strongly associated with higher levels of tTau in the CSF (β = 0.35, SE = 0.13, = 0.008).
CONCLUSION
We provide evidence that CSO-EPVS and CSF-AQP4 might be clinically meaningful biomarkers of glymphatic dysfunction and associated neurodegeneration.
背景
血管周围间隙（PVS）是充满液体的腔隙，会因多种不同情况而扩张。半卵圆中心（CSO）中扩张的血管周围间隙（EPVS）负担过重与神经退行性变有关。此外，在神经退行性痴呆患者中，已发现血管周围间隙边界星形胶质细胞上表达的水通道蛋白4（AQP4）的脑脊液（CSF）水平升高。我们的目的是研究神经退行性疾病与两种假定的类淋巴系统生物标志物：AQP4和EPVS之间的关系。
方法
我们纳入了70名个体，其中54名患有神经退行性疾病的患者和16名患有非退行性疾病的受试者。使用Paradise量表在MRI扫描上对EPVS进行视觉量化。所有受试者均接受腰椎穿刺以测量脑脊液（CSF）中的AQP4水平。还测量了脑脊液中淀粉样蛋白-β-1-42、磷酸化tau蛋白和总tau蛋白（tTau）的水平。在排除异常值后，对年龄、性别、教育程度和病程进行线性回归分析调整。
结果
脑脊液（CSF）-AQP4水平是总EPVS（β = 0.28，标准误差[SE] = 0.08，P = 0.001）、基底神经节EPVS（β = 0.20，SE = 0.08，P = 0.009）和半卵圆中心EPVS（β = 0.37，SE = 0.12，P = 0.003）的独立预测因子。tTau水平可预测CSO-EPVS（β = 0.30，SE = 0.15，P = 0.046）。此外，AQP4水平升高与脑脊液中tTau水平升高密切相关（β = 0.35，SE = 0.13，P = 0.008）。
结论
我们提供的证据表明，CSO-EPVS和CSF-AQP4可能是类淋巴功能障碍和相关神经退行性变具有临床意义的生物标志物。
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