Reyes Ramiro Eduardo Rea, Wilson Rachael E, Langhough Rebecca E, Studer Rachel L, Jonaitis Erin M, Oomens Julie E, Planalp Elizabeth M, Bendlin Barbara B, Chin Nathaniel A, Asthana Sanjay, Zetterberg Henrik, Johnson Sterling C
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI, 53792, USA.
Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, 610 Walnut Street, Madison, WI, 53726, USA.
medRxiv. 2024 Nov 29:2024.11.28.24318162. doi: 10.1101/2024.11.28.24318162.
Targeted proteomic assays may be useful for diagnosing and staging Alzheimer's disease and related dementias (ADRD). We evaluated the performance of a 120-marker central nervous system (CNS) NUcleic acid-Linked Immuno-Sandwich Assay (NULISA) panel in samples spanning the AD spectrum.
Cross-sectional plasma samples (n=252) were analyzed using Alamar's NULISAseq CNS panel. ROC analyses demonstrated NULISAseq-pTau217 accuracy in detecting amyloid (A) and tau (T) PET positivity. Differentially expressed proteins were identified using volcano plots.
NULISAseq-pTau217 accurately classified A/T PET status with ROC AUCs of 0.92/0.86. pTau217 was upregulated in A+, T+, and impaired groups with log2-fold changes of 1.21, 0.57 and 4.63, respectively, compared to A-. Interestingly, pTDP43-409 was also upregulated in the impaired group and correlated with declining hippocampal volume and cognitive trajectories.
This study shows the potential of a targeted proteomics panel for characterizing brain changes pertinent to ADRD. The promising pTDP43-409 findings require further replication.
靶向蛋白质组学检测可能有助于阿尔茨海默病及相关痴呆症（ADRD）的诊断和分期。我们评估了一个包含120种标志物的中枢神经系统（CNS）核酸连接免疫夹心分析（NULISA）检测板在整个AD谱系样本中的性能。
使用阿拉马尔公司的NULISAseq CNS检测板对横断面血浆样本（n = 252）进行分析。ROC分析显示NULISAseq-pTau217在检测淀粉样蛋白（A）和tau蛋白（T）PET阳性方面的准确性。使用火山图鉴定差异表达的蛋白质。
NULISAseq-pTau217能够准确分类A/T PET状态，ROC曲线下面积（AUC）分别为0.92/0.86。与A-组相比，pTau217在A+、T+和受损组中上调，log2倍变化分别为1.21、0.57和4.63。有趣的是，pTDP43-409在受损组中也上调，并且与海马体积减小和认知轨迹下降相关。
本研究显示了靶向蛋白质组学检测板在表征与ADRD相关的脑变化方面的潜力。pTDP43-409的有前景的研究结果需要进一步验证。
