van Waalwijk van Doorn Linda J C, Gispert Juan D, Kuiperij H Bea, Claassen Jurgen A H R, Arighi Andrea, Baldeiras Inês, Blennow Kaj, Bozzali Marco, Castelo-Branco Miguel, Cavedo Enrica, Emek-Savaş Derya D, Eren Erden, Eusebi Paolo, Farotti Lucia, Fenoglio Chiara, Ormaechea Juan Fortea, Freund-Levi Yvonne, Frisoni Giovanni B, Galimberti Daniela, Genc Sermin, Greco Viviana, Hampel Harald, Herukka Sanna-Kaisa, Liu Yawu, Lladó Albert, Lleó Alberto, Nobili Flavio M, Oguz Kader K, Parnetti Lucilla, Pereira João, Picco Agnese, Pikkarainen Maria, de Oliveira Catarina Resende, Saka Esen, Salvadori Nicola, Sanchez-Valle Raquel, Santana Isabel, Scarpini Elio, Scheltens Philip, Soininen Hilkka, Tarducci Roberto, Teunissen Charlotte, Tsolaki Magda, Urbani Andrea, Vilaplana Eduard, Visser Pieter Jelle, Wallin Asa K, Yener Görsev, Molinuevo José L, Meulenbroek Olga, Verbeek Marcel M
Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Centre, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Centre, Radboud University Medical Center, Nijmegen, The Netherlands.
J Alzheimers Dis. 2017;56(2):543-555. doi: 10.3233/JAD-160668.
Cerebrospinal fluid (CSF) biomarkers may support the diagnosis of Alzheimer's disease (AD). We studied if the diagnostic power of AD CSF biomarker concentrations, i.e., Aβ42, total tau (t-tau), and phosphorylated tau (p-tau), is affected by differences in lateral ventricular volume (VV), using CSF biomarker data and magnetic resonance imaging (MRI) scans of 730 subjects, from 13 European Memory Clinics. We developed a Matlab-algorithm for standardized automated segmentation analysis of T1 weighted MRI scans in SPM8 for determining VV, and computed its ratio with total intracranial volume (TIV) as proxy for total CSF volume. The diagnostic power of CSF biomarkers (and their combination), either corrected for VV/TIV ratio or not, was determined by ROC analysis. CSF Aβ42 levels inversely correlated to VV/TIV in the whole study population (Aβ42: r = -0.28; p < 0.0001). For CSF t-tau and p-tau, this association only reached statistical significance in the combined MCI and AD group (t-tau: r = -0.15; p-tau: r = -0.13; both p < 0.01). Correction for differences in VV/TIV improved the differentiation of AD versus controls based on CSF Aβ42 alone (AUC: 0.75 versus 0.81) or in combination with t-tau (AUC: 0.81 versus 0.91). In conclusion, differences in VV may be an important confounder in interpreting CSF Aβ42 levels.
脑脊液（CSF）生物标志物可能有助于阿尔茨海默病（AD）的诊断。我们利用来自13家欧洲记忆诊所的730名受试者的脑脊液生物标志物数据和磁共振成像（MRI）扫描，研究了AD脑脊液生物标志物浓度（即Aβ42、总tau蛋白（t-tau）和磷酸化tau蛋白（p-tau））的诊断能力是否受侧脑室体积（VV）差异的影响。我们开发了一种Matlab算法，用于在SPM8中对T1加权MRI扫描进行标准化自动分割分析以确定VV，并计算其与总颅内体积（TIV）的比值作为总脑脊液体积的替代指标。通过ROC分析确定了校正或未校正VV/TIV比值的脑脊液生物标志物（及其组合）的诊断能力。在整个研究人群中，脑脊液Aβ42水平与VV/TIV呈负相关（Aβ42：r = -0.28；p < 0.0001）。对于脑脊液t-tau和p-tau，这种关联仅在轻度认知障碍（MCI）和AD合并组中达到统计学意义（t-tau：r = -0.15；p-tau：r = -0.13；两者p < 0.01）。校正VV/TIV差异改善了基于单独脑脊液Aβ42（AUC：0.75对0.81）或与t-tau联合（AUC：0.81对0.91）区分AD与对照组的能力。总之，VV差异可能是解释脑脊液Aβ42水平的一个重要混杂因素。
