Department of Neurosurgery, Institute of Clinical Medicine - Neurosurgery, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.
Hydrocephalus Research Unit, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Fluids Barriers CNS. 2022 Feb 5;19(1):11. doi: 10.1186/s12987-022-00309-z.
The relationship between cerebrospinal fluid (CSF) biomarkers and the clinical features of idiopathic normal pressure hydrocephalus (iNPH) has been inconclusive. We aimed to evaluate CSF biomarkers reflecting Alzheimer's disease (AD)-related amyloid β (Aβ) aggregation, tau pathology, neuroinflammation and axonal degeneration in relation to the clinical features of pre- and post-shunt surgery in iNPH patients.
Mini Mental State Examination (MMSE) scores and gait velocity were evaluated pre- and postoperatively in cohorts of 65 Finnish (FIN) and 82 Swedish (SWE) iNPH patients. Lumbar CSF samples were obtained prior to shunt surgery and analysed for soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPβ); amyloid-β isoforms of 42, 40 and 38 (Aβ, Aβ, Aβ); total tau (T-tau); phosphorylated tau (P-tau); neurofilament light (NfL) and monocyte chemoattractant protein 1 (MCP1).
Preoperative patient characteristics showed no significant differences between patients in the FIN and SWE cohorts. Patients in both cohorts had significantly improved gait velocity after shunt surgery (p < 0.0001). Low CSF T-tau and absence of apolipoprotein E ε4 predicted over 20% gait improvement postoperatively (p = 0.043 and p = 0.008). Preoperative CSF T-tau, P-tau and NfL correlated negatively with MMSE scores both pre- (p < 0.01) and post-surgery (p < 0.01). Furthermore, T-tau, NfL and Aβ correlated with MMSE outcomes (p < 0.05). Low preoperative CSF P-tau (p = 0.001) and T-tau with NfL (p < 0.001 and p = 0.049) best predicted pre- and postoperative MMSE scores greater than or equal to 26.
CSF biomarkers of neurodegeneration appeared to correlate with pre- and postoperative cognition, providing a window into neuropathological processes. In addition, preoperative CSF neurodegeneration biomarkers may have potential in the prediction of gait and cognitive outcomes after shunt surgery.
脑脊髓液（CSF）生物标志物与特发性正常压力脑积水（iNPH）的临床特征之间的关系尚无定论。我们旨在评估 CSF 生物标志物，以反映阿尔茨海默病（AD）相关淀粉样β（Aβ）聚集、tau 病理学、神经炎症和轴突退化与 iNPH 患者术前和术后分流术的临床特征的关系。
我们评估了芬兰（FIN）和瑞典（SWE）队列的 65 名 iNPH 患者和 82 名 iNPH 患者术前和术后的简易精神状态检查（MMSE）评分和步态速度。在分流术前获得腰椎 CSF 样本，并分析可溶性淀粉样前体蛋白α（sAPPα）和β（sAPPβ）；42、40 和 38 种淀粉样-β异构体（Aβ、Aβ、Aβ）；总 tau（T-tau）；磷酸化 tau（P-tau）；神经丝轻链（NfL）和单核细胞趋化蛋白 1（MCP1）。
FIN 和 SWE 队列患者的术前患者特征无显著差异。两组患者分流术后的步态速度均显著改善（p<0.0001）。低 CSF T-tau 和无载脂蛋白 E ε4 预测术后 20%以上的步态改善（p=0.043 和 p=0.008）。术前 CSF T-tau、P-tau 和 NfL 与 MMSE 评分呈负相关，术前（p<0.01）和术后（p<0.01）均如此。此外，T-tau、NfL 和 Aβ 与 MMSE 结果相关（p<0.05）。低术前 CSF P-tau（p=0.001）和 T-tau 与 NfL（p<0.001 和 p=0.049）最佳预测术前和术后 MMSE 评分≥26。
神经退行性变的 CSF 生物标志物似乎与术前和术后认知相关，为神经病理学过程提供了一个窗口。此外，术前 CSF 神经退行性变生物标志物可能具有预测分流术后步态和认知结果的潜力。
