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.
J Alzheimers Dis. 2023;91(1):305-319. doi: 10.3233/JAD-220652.
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.
Here we aim to provide conversion factors for clinical and research use between V-CSF and L-CSF.
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.
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).
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.
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。
本研究旨在提供 V-CSF 和 L-CSF 之间的临床和研究转换因子。
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。
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。
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。
