Giacomucci Giulia, Mazzeo Salvatore, Crucitti Chiara, Ingannato Assunta, Bagnoli Silvia, Padiglioni Sonia, Galdo Giulia, Emiliani Filippo, Frigerio Daniele, Moschini Valentina, Morinelli Carmen, Sorbi Sandro, Bessi Valentina, Nacmias Benedetta
Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.
Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy; IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy.
J Neurol Sci. 2023 Oct 15;453:120805. doi: 10.1016/j.jns.2023.120805. Epub 2023 Sep 12.
The aim of this study is to investigate the role of plasma phosphorylated tau (p-tau) 181 as a potential biomarker for Alzheimer's Disease (AD) pathology in the early stages of the disease, as a valuable marker for tauopathy.
Thirty-three Subjective Cognitive Decline (SCD), 32 Mild Cognitive Impairment (MCI) and 14 AD demented (AD-d) patients underwent plasma p-tau181 analysis with SiMoA assay. Twenty-six SCD, 32 MCI and 14 AD-d patients also underwent CSF biomarkers analysis (Aβ1-42, Aβ1-42/1-40, p-tau, t-tau) and were classified as carriers of AD pathology (AP+) when A+ was associated with T+ (regardless of N), or non-carriers (AP-) when they were A- (regardless of T and N), or A+/T-/N-, or A+/T-/N+ according to the A/T(N) system.
Plasma p-tau181 levels were higher in SCD AP+ than in SCD AP- (2.85 ± 0.53 vs 1.73 ± 0.64, p < 0.001), and in MCI AP+ than in MCI AP- (4.03 ± 1.07 vs 2.04 ± 0.87, p < 0.001). In a multivariate linear regression analysis, AP status was the only variable that influenced plasma p-tau181 (B = 1.670 [95% CI 1.097:2.244], p < 0.001). Plasma p-tau181 was highly accurate for discriminating between AP+ and AP- patients (AUC = 0.910). We identified a cut-off level of 2.69 pg/mL to distinguish between AP+ and AP- (sensibility 0.86, specificity 0.82, PPV 75.00% NPV 90.32%).
Plasma p-tau181 levels were influenced by the presence of underlying AD pathology, independently from the cognitive status and were highly accurate in differentiating SCD-MCI patients who were carriers of AD pathology from non-carriers. Plasma p-tau181 might be a promising non-invasive biomarker of AD pathology at a very early stage.
本研究旨在探讨血浆磷酸化tau蛋白（p-tau）181作为阿尔茨海默病（AD）早期病理潜在生物标志物以及tau蛋白病有价值标志物的作用。
33例主观认知下降（SCD）患者、32例轻度认知障碍（MCI）患者和14例AD痴呆（AD-d）患者接受了采用SiMoA检测法的血浆p-tau181分析。26例SCD患者、32例MCI患者和14例AD-d患者还接受了脑脊液生物标志物分析（Aβ1-42、Aβ1-42/1-40、p-tau、总tau蛋白[t-tau]），并根据A/T（N）系统被分类为AD病理携带者（AP+），即A+与T+相关时（无论N情况如何）；或非携带者（AP-），即A-时（无论T和N情况如何），或A+/T-/N-，或A+/T-/N+。
SCD患者中AP+组的血浆p-tau181水平高于AP-组（2.85±0.53对1.73±0.64，p<0.001），MCI患者中AP+组高于AP-组（4.03±1.07对2.04±0.87，p<0.001）。在多变量线性回归分析中，AP状态是影响血浆p-tau181的唯一变量（B=1.670[95%CI 1.097:2.244]，p<0.001）。血浆p-tau181在区分AP+和AP-患者方面具有高度准确性（AUC=0.910）。我们确定区分AP+和AP-的临界值为2.69 pg/mL（敏感性0.86，特异性0.82，阳性预测值75.00%，阴性预测值90.32%）。
血浆p-tau181水平受潜在AD病理存在的影响，独立于认知状态，并且在区分AD病理携带者与非携带者的SCD-MCI患者方面具有高度准确性。血浆p-tau181可能是AD极早期病理一种有前景的非侵入性生物标志物。
