特发性正常压力脑积水患者脑室和腰椎脑脊液中阿尔茨海默病相关生物标志物的一致性。

Concordance of Alzheimer's Disease-Related Biomarkers Between Intraventricular and Lumbar Cerebrospinal Fluid in Idiopathic Normal Pressure Hydrocephalus.

机构信息

Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland and Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland.

UCB Biopharma SRL, Braine-l'Alleud, Belgium.

出版信息

J Alzheimers Dis. 2023;91(1):305-319. doi: 10.3233/JAD-220652.

DOI:10.3233/JAD-220652

PMID:36404546

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9881032/

Abstract

BACKGROUND

Alzheimer's disease cerebrospinal fluid (CSF) biomarkers amyloid-β 1-42 (Aβ42), total tau (T-tau), and phosphorylated tau 181 (P-tau181) are widely used. However, concentration gradient of these biomarkers between intraventricular (V-CSF) and lumbar CSF (L-CSF) has been demonstrated in idiopathic normal pressure hydrocephalus (iNPH), potentially affecting clinical utility.

OBJECTIVE

Here we aim to provide conversion factors for clinical and research use between V-CSF and L-CSF.

METHODS

Altogether 138 iNPH patients participated. L-CSF samples were obtained prior to shunt surgery. Intraoperative V-CSF samples were obtained from 97 patients. Post-operative follow-up L- and V-CSF (shunt reservoir) samples of 41 patients were obtained 1-73 months after surgery and then after 3, 6, and 18 months. CSF concentrations of Aβ42, T-tau, and P-tau181 were analyzed using commercial ELISA assays.

RESULTS

Preoperative L-CSF Aβ42, T-tau, and P-tau181 correlated to intraoperative V-CSF (ρ= 0.34-0.55, p < 0.001). Strong correlations were seen between postoperative L- and V-CSF for all biomarkers in every follow-up sampling point (ρs Aβ42: 0.77-0.88, T-tau: 0.91-0.94, P-tau181: 0.94-0.96, p < 0.0001). Regression equations were determined for intraoperative V- and preoperative L-CSF (Aβ42: V-CSF = 185+0.34L-CSF, T-tau: Ln(V-CSF) = 3.11+0.49Ln(L-CSF), P-tau181: V-CSF = 8.2+0.51L-CSF), and for postoperative V- and L-CSF (Aβ42: V-CSF = 86.7+0.75L-CSF, T-tau: V-CSF = 86.9+0.62L-CSF, P-tau181: V-CSF = 2.6+0.74L-CSF).

CONCLUSION

Aβ42, T-tau, and P-tau181 correlate linearly in-between V- and L-CSF, even stronger after CSF shunt surgery. Equations presented here, provide a novel tool to use V-CSF for diagnostic and prognostic entities relying on the L-CSF concentrations and can be applicable to clinical use when L-CSF samples are not available or less invasively obtained shunt reservoir samples should be interpreted.

摘要

背景

阿尔茨海默病的脑脊液（CSF）生物标志物β淀粉样蛋白 1-42（Aβ42）、总tau（T-tau）和磷酸化 tau 181（P-tau181）被广泛应用。然而，在特发性正常压力脑积水（iNPH）中已经证明了这些生物标志物在脑室（V-CSF）和腰椎 CSF（L-CSF）之间存在浓度梯度，这可能会影响其临床应用。

目的

本研究旨在提供 V-CSF 和 L-CSF 之间的临床和研究转换因子。

方法

共纳入 138 例 iNPH 患者。所有患者在分流手术前均采集 L-CSF 样本，97 例患者在手术过程中采集 V-CSF 样本。41 例患者在分流术后 1-73 个月后进行了术后 L-CSF 和 V-CSF（分流储液池）的随访采集，然后在术后 3、6 和 18 个月进行了随访。采用商业 ELISA 试剂盒检测 CSF 中 Aβ42、T-tau 和 P-tau181 的浓度。

结果

术前 L-CSF 的 Aβ42、T-tau 和 P-tau181 与术中 V-CSF 呈正相关（ρ=0.34-0.55，p<0.001）。在每个随访采样点，术后 L-CSF 和 V-CSF 之间的所有生物标志物均呈强相关性（Aβ42：ρ=0.77-0.88，T-tau：ρ=0.91-0.94，P-tau181：ρ=0.94-0.96，p<0.0001）。确定了术中 V-CSF 和术前 L-CSF（Aβ42：V-CSF=185+0.34L-CSF，T-tau：Ln（V-CSF）=3.11+0.49Ln（L-CSF），P-tau181：V-CSF=8.2+0.51L-CSF）以及术后 V-CSF 和 L-CSF（Aβ42：V-CSF=86.7+0.75L-CSF，T-tau：V-CSF=86.9+0.62L-CSF，P-tau181：V-CSF=2.6+0.74L-CSF）之间的回归方程。

结论

Aβ42、T-tau 和 P-tau181 在 V-CSF 和 L-CSF 之间呈线性相关，在 CSF 分流手术后相关性更强。本研究提出的方程为基于 L-CSF 浓度使用 V-CSF 进行诊断和预后实体提供了一种新的工具，当无法获得 L-CSF 样本或需要获取侵入性更小的分流储液池样本时，这些方程可以应用于临床。