CSF 中 tau 磷酸化的 T217 和 T205 占有率代表了阿尔茨海默病中淀粉样蛋白和 tau 病理的改进生物标志物。

CSF tau phosphorylation occupancies at T217 and T205 represent improved biomarkers of amyloid and tau pathology in Alzheimer's disease.

机构信息

Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.

Tracy Family SILQ Center for Neurodegenerative Biology, St. Louis, MO, USA.

出版信息

Nat Aging. 2023 Apr;3(4):391-401. doi: 10.1038/s43587-023-00380-7. Epub 2023 Mar 13.

DOI:10.1038/s43587-023-00380-7

PMID:37117788

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10154225/

Abstract

Cerebrospinal fluid (CSF) amyloid-β peptide (Aβ)42/Aβ40 and the concentration of tau phosphorylated at site 181 (p-tau181) are well-established biomarkers of Alzheimer's disease (AD). The present study used mass spectrometry to measure concentrations of nine phosphorylated and five nonphosphorylated tau species and phosphorylation occupancies (percentage phosphorylated/nonphosphorylated) at ten sites. In the present study we show that, in 750 individuals with a median age of 71.2 years, CSF pT217/T217 predicted the presence of brain amyloid by positron emission tomography (PET) slightly better than Aβ42/Aβ40 (P = 0.02). Furthermore, for individuals with positive brain amyloid by PET (n = 263), CSF pT217/T217 was more strongly correlated with the amount of amyloid (Spearman's ρ = 0.69) than Aβ42/Aβ40 (ρ = -0.42, P < 0.0001). In two independent cohorts of participants with symptoms of AD dementia (n = 55 and n = 90), CSF pT217/T217 and pT205/T205 were better correlated with tau PET measures than CSF p-tau181 concentration. These findings suggest that CSF pT217/T217 and pT205/T205 represent improved CSF biomarkers of amyloid and tau pathology in AD.

摘要

脑脊液（CSF）淀粉样β肽（Aβ）42/Aβ40 和磷酸化丝氨酸 181 位点的 tau（p-tau181）浓度是阿尔茨海默病（AD）的既定生物标志物。本研究使用质谱法测量了 9 种磷酸化和 5 种非磷酸化 tau 物种以及 10 个位点的磷酸化占有率（磷酸化/非磷酸化的百分比）。在本研究中，我们发现，在 750 名中位年龄为 71.2 岁的个体中，CSF pT217/T217 通过正电子发射断层扫描（PET）预测脑淀粉样蛋白的存在情况略优于 Aβ42/Aβ40（P=0.02）。此外，对于 PET 阳性的脑淀粉样蛋白个体（n=263），CSF pT217/T217 与淀粉样蛋白的量之间的相关性更强（Spearman's ρ=0.69），而 Aβ42/Aβ40 则较弱（ρ=-0.42，P<0.0001）。在两个具有 AD 痴呆症状的参与者独立队列中（n=55 和 n=90），CSF pT217/T217 和 pT205/T205 与 tau PET 测量的相关性优于 CSF p-tau181 浓度。这些发现表明，CSF pT217/T217 和 pT205/T205 代表了 AD 中淀粉样蛋白和 tau 病理的改进的 CSF 生物标志物。