Optimal blood tau species for the detection of Alzheimer's disease neuropathology: an immunoprecipitation mass spectrometry and autopsy study.
Optimal blood tau species for the detection of Alzheimer's disease neuropathology: an immunoprecipitation mass spectrometry and autopsy study.
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检测阿尔茨海默病神经病理学的最佳tau血型：免疫沉淀质谱学和尸检研究。
DOI：
10.1007/s00401-023-02660-3
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发表时间：
2023-12-30
影响因子：
12.7
通讯作者：
中科院分区：
文献类型：
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作者：
血浆与尸检研究对于血液生物标志物的验证以及理解它们与阿尔茨海默病（AD）病理的关系至关重要。关于磷酸化tau蛋白（p - tau）的此类研究很少，现有的研究对不同的p - tau变体进行的比较有限或没有比较。本研究首次使用免疫沉淀质谱法（IP - MS）比较了八种不同血浆tau蛋白种类在预测经尸检确诊的AD方面的准确性。样本包括来自波士顿大学阿尔茨海默病研究中心的123名参与者（AD = 69人，非AD = 54人），他们有生前可用的血浆样本并捐赠了大脑。对接近死亡时的血浆样本通过靶向IP - MS分析六种不同的胰蛋白酶磷酸化（p - tau - 181、199、202、205、217、231）以及两种非磷酸化tau（195 - 205、212 - 221）肽段。采用美国国立衰老研究所 - 里根研究所（NIA - Reagan Institute）标准对AD进行神经病理学诊断。二元逻辑回归检验了每种血浆肽段与尸检确诊的AD状态之间的关联。使用逻辑回归模型的预测概率生成受试者工作特征曲线下面积（AUC）统计数据。优势比（OR）用于研究不同血浆tau蛋白种类与CERAD和Braak分级之间的关联。与非AD相比，所有tau蛋白种类在AD中均增加，但p - tau217、p - tau205和p - tau231显示出最高的倍数变化。血浆p - tau217（AUC = 89.8）、p - tau231（AUC = 83.4）和p - tau205（AUC = 81.3）在区分AD和非AD脑捐赠者方面都具有极高的准确性，即使在临床痴呆评定量表（CDR）<1的人群中也是如此。此外，p - tau217、p - tau205和p - tau231与CERAD（ORp - tau217 = 15.29，ORp - tau205 = 5.05和ORp - tau231 = 3.86）和Braak分期（ORp - tau217 = 14.29，ORp - tau205 = 5.27和ORp - tau231 = 4.02）都显示出最高的优势比，但在通过神经病理学检查确定的不同淀粉样蛋白和tau阶段呈现出升高的水平。我们的研究结果支持血浆p - tau217是检测AD脑病理最有前景的p - tau种类。血浆p - tau231和p - tau205可能还可作为疾病不同阶段的标志物。
网络版包含补充材料，可在10.1007/s00401 - 023 - 02660 - 3获取。
Plasma-to-autopsy studies are essential for validation of blood biomarkers and understanding their relation to Alzheimer’s disease (AD) pathology. Few such studies have been done on phosphorylated tau (p-tau) and those that exist have made limited or no comparison of the different p-tau variants. This study is the first to use immunoprecipitation mass spectrometry (IP-MS) to compare the accuracy of eight different plasma tau species in predicting autopsy-confirmed AD. The sample included 123 participants (AD = 69, non-AD = 54) from the Boston University Alzheimer’s disease Research Center who had an available ante-mortem plasma sample and donated their brain. Plasma samples proximate to death were analyzed by targeted IP-MS for six different tryptic phosphorylated (p-tau-181, 199, 202, 205, 217, 231), and two non-phosphorylated tau (195–205, 212–221) peptides. NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Binary logistic regressions tested the association between each plasma peptide and autopsy-confirmed AD status. Area under the receiver operating curve (AUC) statistics were generated using predicted probabilities from the logistic regression models. Odds Ratio (OR) was used to study associations between the different plasma tau species and CERAD and Braak classifications. All tau species were increased in AD compared to non-AD, but p-tau217, p-tau205 and p-tau231 showed the highest fold-changes. Plasma p-tau217 (AUC = 89.8), p-tau231 (AUC = 83.4), and p-tau205 (AUC = 81.3) all had excellent accuracy in discriminating AD from non-AD brain donors, even among those with CDR < 1). Furthermore, p-tau217, p-tau205 and p-tau231 showed the highest ORs with both CERAD (ORp-tau217 = 15.29, ORp-tau205 = 5.05 and ORp-tau231 = 3.86) and Braak staging (ORp-tau217 = 14.29, ORp-tau205 = 5.27 and ORp-tau231 = 4.02) but presented increased levels at different amyloid and tau stages determined by neuropathological examination. Our findings support plasma p-tau217 as the most promising p-tau species for detecting AD brain pathology. Plasma p-tau231 and p-tau205 may additionally function as markers for different stages of the disease. The online version contains supplementary material available at 10.1007/s00401-023-02660-3.
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DOI：
10.1084/jem.20200861
发表时间：
2020-11-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Barthélemy NR;Horie K;Sato C;Bateman RJ
通讯作者：
Bateman RJ
影响因子：
12.7
作者：
Ashton NJ;Pascoal TA;Karikari TK;Benedet AL;Lantero-Rodriguez J;Brinkmalm G;Snellman A;Schöll M;Troakes C;Hye A;Gauthier S;Vanmechelen E;Zetterberg H;Rosa-Neto P;Blennow K
通讯作者：
Blennow K
影响因子：
9.9
作者：
Mattsson N;Zetterberg H;Janelidze S;Insel PS;Andreasson U;Stomrud E;Palmqvist S;Baker D;Tan Hehir CA;Jeromin A;Hanlon D;Song L;Shaw LM;Trojanowski JQ;Weiner MW;Hansson O;Blennow K;ADNI Investigators
通讯作者：
ADNI Investigators
影响因子：
2.1
作者：
Mock, Charles;Teylan, Merilee;Kukull, Walter
通讯作者：
Kukull, Walter
DOI：
10.1038/s43587-023-00471-5
发表时间：
2023-09
期刊：
NATURE AGING
影响因子：
--
作者：
Brum, Wagner S.;Cullen, Nicholas C.;Janelidze, Shorena;Ashton, Nicholas J.;Zimmer, Eduardo R.;Therriault, Joseph;Benedet, Andrea L.;Rahmouni, Nesrine;Tissot, Cecile;Stevenson, Jenna;Servaes, Stijn;Triana-Baltzer, Gallen;Kolb, Hartmuth C.;Palmqvist, Sebastian;Stomrud, Erik;Rosa-Neto, Pedro;Blennow, Kaj;Hansson, Oskar
通讯作者：
Hansson, Oskar