Department of Neurology, Washington University in St. Louis, St. Louis, Missouri, USA.
Department of Radiology, Washington University in St. Louis, St. Louis, Missouri, USA.
Alzheimers Dement. 2024 Sep;20(9):6365-6373. doi: 10.1002/alz.14132. Epub 2024 Jul 23.
Cerebrospinal fluid (CSF) tau phosphorylation at multiple sites is associated with cortical amyloid and other pathologic changes in Alzheimer's disease. These relationships can be non-linear. We used an artificial neural network to assess the ability of 10 different CSF tau phosphorylation sites to predict continuous amyloid positron emission tomography (PET) values.
CSF tau phosphorylation occupancies at 10 sites (including pT181/T181, pT217/T217, pT231/T231 and pT205/T205) were measured by mass spectrometry in 346 individuals (57 cognitively impaired, 289 cognitively unimpaired). We generated synthetic amyloid PET scans using biomarkers and evaluated their performance.
Concentration of CSF pT217/T217 had low predictive error (average error: 13%), but also a low predictive range (ceiling 63 Centiloids). CSF pT231/T231 has slightly higher error (average error: 19%) but predicted through a greater range (87 Centiloids).
Tradeoffs exist in biomarker selection. Some phosphorylation sites offer greater concordance with amyloid PET at lower levels, while others perform better over a greater range.
Novel pTau isoforms can predict cortical amyloid burden. pT217/T217 accurately predicts cortical amyloid burden in low-amyloid individuals. Traditional CSF biomarkers correspond with higher levels of amyloid.
脑脊液（CSF）中多个部位的 tau 磷酸化与阿尔茨海默病的皮质淀粉样蛋白和其他病理改变有关。这些关系可能是非线性的。我们使用人工神经网络来评估 10 种不同 CSF tau 磷酸化部位预测连续淀粉样蛋白正电子发射断层扫描（PET）值的能力。
通过质谱法测量了 346 个人（57 名认知障碍，289 名认知未受损）的 10 个部位（包括 pT181/T181、pT217/T217、pT231/T231 和 pT205/T205）的 CSF tau 磷酸化占有率。我们使用生物标志物生成了合成的淀粉样蛋白 PET 扫描，并评估了它们的性能。
CSF pT217/T217 的浓度具有较低的预测误差（平均误差：13%），但预测范围也较低（上限为 63 百分位数）。CSF pT231/T231 的误差略高（平均误差：19%），但通过更大的范围（87 百分位数）进行预测。
生物标志物的选择存在权衡。一些磷酸化位点在较低水平下与淀粉样蛋白 PET 具有更高的一致性，而其他位点在更大范围内表现更好。
新型 pTau 异构体可以预测皮质淀粉样蛋白负担。pT217/T217 可准确预测低淀粉样蛋白个体的皮质淀粉样蛋白负担。传统的 CSF 生物标志物与更高水平的淀粉样蛋白相对应。
