Department of Medical Sciences, Neurology, Uppsala University, Uppsala, Sweden.
Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
Fluids Barriers CNS. 2022 Jul 17;19(1):59. doi: 10.1186/s12987-022-00353-9.
Levels of the biomarkers amyloid-β 1-42 (Aβ42), tau and phosphorylated tau (p-tau) are decreased in the cerebrospinal fluid (CSF) of patients with idiopathic normal pressure hydrocephalus (iNPH). The mechanism behind this is unknown, but one potential explanation is dilution by excessive CSF volumes. The aim of this study was to investigate the presence of a dilution effect, by studying the relationship between ventricular volume (VV) and the levels of the CSF biomarkers.
In this cross-sectional observational study, preoperative magnetic resonance imaging (MRI) and lumbar CSF was acquired from 136 patients with a median age of 76 years, 89 men and 47 females, selected for surgical treatment for iNPH. The CSF volume of the lateral and third ventricles was segmented on MRI and related to preoperative concentrations of Aβ42, tau and p-tau.
In the total sample VV (Median 140.7 mL) correlated weakly (r = - 0.17) with Aβ42 (Median 534 pg/mL), but not with tau (Median 216 pg/mL) nor p-tau (Median 31 pg/mL). In a subgroup analysis, the correlation between VV and Aβ42 was only present in the male group (r = - 0.22, p = 0.038). Further, Aβ42 correlated positively with tau (r = 0.30, p = 0.004) and p-tau (r = 0.26, p = 0.012) in males but not in females.
The findings did not support a major dilution effect in iNPH, at least not in females. The only result in favor for dilution was a weak negative correlation between VV and Aβ42 but not with the other lumbar CSF biomarkers. The different results between males and females suggest that future investigations of the CSF pattern in iNPH would gain from sex-based subgroup analysis.
特发性正常压力脑积水（iNPH）患者的脑脊液（CSF）中淀粉样蛋白-β 1-42（Aβ42）、tau 和磷酸化 tau（p-tau）水平降低。其背后的机制尚不清楚，但一种潜在的解释是 CSF 体积过大导致的稀释。本研究旨在通过研究脑室容积（VV）与 CSF 生物标志物水平之间的关系，探讨是否存在稀释效应。
本横断面观察性研究纳入了 136 名平均年龄为 76 岁（中位数）的患者，其中男性 89 名，女性 47 名，均因 iNPH 接受手术治疗。采集术前 MRI 和腰椎 CSF。对 MRI 上的侧脑室和第三脑室容积进行分割，并与术前 Aβ42、tau 和 p-tau 的浓度相关联。
在整个样本中，VV（中位数 140.7ml）与 Aβ42（中位数 534pg/ml）呈弱相关（r=-0.17），但与 tau（中位数 216pg/ml）和 p-tau（中位数 31pg/ml）无关。在亚组分析中，只有男性组 VV 与 Aβ42 之间存在相关性（r=-0.22，p=0.038）。此外，在男性中，Aβ42 与 tau（r=0.30，p=0.004）和 p-tau（r=0.26，p=0.012）呈正相关，但在女性中则没有相关性。
研究结果不支持 iNPH 存在主要的稀释效应，至少在女性中不存在。唯一支持稀释的结果是 VV 与 Aβ42 之间存在微弱的负相关，但与其他腰椎 CSF 生物标志物无关。男性和女性之间的结果不同表明，未来研究 iNPH 的 CSF 模式时，基于性别的亚组分析可能会有所帮助。
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