• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

一种改进的免疫测定法可检测人体生物流体中的β淀粉样蛋白寡聚体：其脑脊液水平随tau蛋白和磷酸化tau蛋白水平升高而升高。

An improved immunoassay detects Aβ oligomers in human biofluids: their CSF levels rise with tau and phosphotau levels.

作者信息

Yang Ting, Xu Yi Ran, Jin Shanxue, Ramalingam Nagendran, Bellier Jean-Pierre, Lish Alexandra M, Ostaszewski Beth L, Young-Pearse Tracy, Liu Lei, Yang Hyun-Sik, Chhatwal Jasmeer P, Lawton Trebor L, Selkoe Dennis J

机构信息

Department of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Boston, MA, 02115, USA.

Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.

出版信息

Alzheimers Res Ther. 2025 Jul 12;17(1):153. doi: 10.1186/s13195-025-01802-x.

DOI:10.1186/s13195-025-01802-x
PMID:40646564
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12255133/
Abstract

BACKGROUND

Diffusible Aβ oligomers (oAβ) confer cytotoxicity in Alzheimer's disease. The dynamic complexity of this hydrophobic analyte means few immunoassays exist to quantify oAβ in CSF and plasma.

METHODS

We characterized antibody 71A1 to a cyclized dimer of Aβ9-18 for oAβ preference over monomers by surface plasmon resonance. We improved an earlier bead-based immunoassay by using 71A1 streptavidin plates for capture and N-terminal antibody 3D6 for detection. Numerous controls systematically validated accuracy.

RESULTS

71A1 showed highly selective binding kinetics to Aβ oligomers over monomers. It enriched bioactive oligomers from AD brain that altered neuronal excitatory currents and calcium transients. 71A1/3D6 immunoassay exhibited specificity and reproducibility in human biofluids. CSF oAβ levels correlated positively with CSF tau and phosphorylated-tau-181. APP and PS1 FAD mutations increased oAβ levels in human neuronal media.

CONCLUSIONS

CSF oAβ levels rise in concert with rising tau levels. A new plate-based ELISA offers improved consistency, less sample volume, and lower cost, thus better suited to quantify this challenging analyte.

摘要

背景

可扩散的Aβ寡聚体（oAβ）在阿尔茨海默病中具有细胞毒性。这种疏水性分析物的动态复杂性意味着用于定量脑脊液和血浆中oAβ的免疫测定方法很少。

方法

我们通过表面等离子体共振表征了针对Aβ9 - 18环化二聚体的抗体71A1对oAβ相对于单体的偏好。我们通过使用71A1链霉亲和素板进行捕获和N端抗体3D6进行检测，改进了早期基于磁珠的免疫测定方法。大量对照系统地验证了准确性。

结果

71A1对Aβ寡聚体显示出比对单体更高的选择性结合动力学。它从AD大脑中富集了改变神经元兴奋性电流和钙瞬变的生物活性寡聚体。71A1/3D6免疫测定在人体生物流体中表现出特异性和可重复性。脑脊液oAβ水平与脑脊液tau和磷酸化tau - 181呈正相关。APP和PS1家族性阿尔茨海默病（FAD）突变会增加人神经元培养基中的oAβ水平。

结论

脑脊液oAβ水平与tau水平升高同步上升。一种新的基于平板的酶联免疫吸附测定（ELISA）提供了更高的一致性、更少的样本量和更低的成本，因此更适合定量这种具有挑战性的分析物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3c6/12255133/282eff06dde9/13195_2025_1802_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3c6/12255133/d78da769a775/13195_2025_1802_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3c6/12255133/92987afa4d11/13195_2025_1802_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3c6/12255133/1b72b9d5400f/13195_2025_1802_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3c6/12255133/4a38829388d0/13195_2025_1802_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3c6/12255133/739f81a8f35c/13195_2025_1802_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3c6/12255133/282eff06dde9/13195_2025_1802_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3c6/12255133/d78da769a775/13195_2025_1802_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3c6/12255133/92987afa4d11/13195_2025_1802_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3c6/12255133/1b72b9d5400f/13195_2025_1802_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3c6/12255133/4a38829388d0/13195_2025_1802_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3c6/12255133/739f81a8f35c/13195_2025_1802_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3c6/12255133/282eff06dde9/13195_2025_1802_Fig6_HTML.jpg

相似文献

1
An improved immunoassay detects Aβ oligomers in human biofluids: their CSF levels rise with tau and phosphotau levels.一种改进的免疫测定法可检测人体生物流体中的β淀粉样蛋白寡聚体：其脑脊液水平随tau蛋白和磷酸化tau蛋白水平升高而升高。
Alzheimers Res Ther. 2025 Jul 12;17(1):153. doi: 10.1186/s13195-025-01802-x.
2
CSF tau and the CSF tau/ABeta ratio for the diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI).脑脊液tau蛋白及脑脊液tau蛋白与β淀粉样蛋白比值在轻度认知障碍（MCI）患者中用于诊断阿尔茨海默病性痴呆及其他痴呆。
Cochrane Database Syst Rev. 2017 Mar 22;3(3):CD010803. doi: 10.1002/14651858.CD010803.pub2.
3
Insulin-like growth factor binding protein-2 in at-risk adults and autopsy-confirmed Alzheimer brains.高危成年人及尸检确诊的阿尔茨海默病患者大脑中的胰岛素样生长因子结合蛋白-2
Brain. 2024 May 3;147(5):1680-1695. doi: 10.1093/brain/awad398.
4
Acute targeting of N-terminal tau protein has long-lasting beneficial effects in Tg2576 APP/Aβ mouse model by reducing cognitive impairment, cerebral Aβ-amyloidosis, synaptic remodeling and microgliosis later in life.在Tg2576 APP/Aβ小鼠模型中，对N端tau蛋白进行急性靶向作用可通过减轻晚年的认知障碍、脑Aβ淀粉样变性、突触重塑和小胶质细胞增生，产生长期有益影响。
Acta Neuropathol Commun. 2025 May 29;13(1):121. doi: 10.1186/s40478-025-02022-y.
5
An ultra-sensitive immunoassay detects and quantifies soluble Aβ oligomers in human plasma.一种超敏免疫分析检测和定量人血浆中的可溶性 Aβ 寡聚物。
Alzheimers Dement. 2022 Jun;18(6):1186-1202. doi: 10.1002/alz.12457. Epub 2021 Sep 22.
6
Brain-derived tau: a novel blood-based biomarker for Alzheimer's disease-type neurodegeneration.脑源性 tau：阿尔茨海默病型神经退行性变的新型基于血液的生物标志物。
Brain. 2023 Mar 1;146(3):1152-1165. doi: 10.1093/brain/awac407.
7
Amyloid-β peptide signature associated with cerebral amyloid angiopathy in familial Alzheimer's disease with APPdup and Down syndrome.与 APP 双突变和唐氏综合征家族性阿尔茨海默病相关的脑淀粉样血管病的淀粉样-β肽特征。
Acta Neuropathol. 2024 Jul 18;148(1):8. doi: 10.1007/s00401-024-02756-4.
8
Two-Year Prognostic Utility of Plasma p217+tau across the Alzheimer's Continuum.血浆p217 + tau在阿尔茨海默病连续体中的两年预后效用
J Prev Alzheimers Dis. 2023;10(4):828-836. doi: 10.14283/jpad.2023.83.
9
Extracellular vesicles from hiPSC-derived NSCs protect human neurons against Aβ-42 oligomers induced neurodegeneration, mitochondrial dysfunction and tau phosphorylation.来自人诱导多能干细胞衍生神经干细胞的细胞外囊泡可保护人类神经元免受Aβ-42寡聚体诱导的神经退行性变、线粒体功能障碍和tau蛋白磷酸化。
Stem Cell Res Ther. 2025 Apr 18;16(1):191. doi: 10.1186/s13287-025-04324-3.
10
Elevated CSF GAP-43 in Mild Cognitive Impairment Linked to Cognitive Impairment Through Increased Amyloid-β Accumulation, with a Shift to Reduced Amyloid-β Accumulation in Alzheimer's Disease.轻度认知障碍患者脑脊液中生长相关蛋白43（GAP-43）升高，通过淀粉样β蛋白（Aβ）积累增加与认知障碍相关，而在阿尔茨海默病中则转变为Aβ积累减少。
J Mol Neurosci. 2025 Mar 20;75(2):39. doi: 10.1007/s12031-025-02333-8.

本文引用的文献

1
β-Amyloid species production and tau phosphorylation in iPSC-neurons with reference to neuropathologically characterized matched donor brains.β-淀粉样蛋白种的产生和 iPSC 神经元中的 tau 磷酸化与神经病理学特征匹配的供体大脑有关。
J Neuropathol Exp Neurol. 2024 Sep 1;83(9):772-782. doi: 10.1093/jnen/nlae053.
2
Clinical evaluation of a novel plasma pTau217 electrochemiluminescence immunoassay in Alzheimer's disease.新型血浆 pTau217 电化学发光免疫分析在阿尔茨海默病中的临床评估。
Sci Rep. 2024 Jan 5;14(1):629. doi: 10.1038/s41598-024-51334-x.
3
Trajectories of CSF and plasma biomarkers across Alzheimer's disease continuum: disease staging by NF-L, p-tau181, and GFAP.
阿尔茨海默病连续体中 CSF 和血浆生物标志物的轨迹：通过 NF-L、p-tau181 和 GFAP 进行疾病分期。
Neurobiol Dis. 2023 Dec;189:106356. doi: 10.1016/j.nbd.2023.106356. Epub 2023 Nov 15.
4
Abundant Aβ fibrils in ultracentrifugal supernatants of aqueous extracts from Alzheimer's disease brains.阿尔茨海默病脑中水提物经超速离心上清液中富含 Aβ 纤维。
Neuron. 2023 Jul 5;111(13):2012-2020.e4. doi: 10.1016/j.neuron.2023.04.007. Epub 2023 May 10.
5
The dynamics of plasma biomarkers across the Alzheimer's continuum.阿尔茨海默病连续体中血浆生物标志物的动态变化。
Alzheimers Res Ther. 2023 Feb 8;15(1):31. doi: 10.1186/s13195-023-01174-0.
6
Assessment of Plasma and Cerebrospinal Fluid Biomarkers in Different Stages of Alzheimer's Disease and Frontotemporal Dementia.评估阿尔茨海默病和额颞叶痴呆不同阶段的血浆和脑脊液生物标志物。
Int J Mol Sci. 2023 Jan 8;24(2):1226. doi: 10.3390/ijms24021226.
7
Dynamic physiological α-synuclein S129 phosphorylation is driven by neuronal activity.动态生理性α-突触核蛋白S129磷酸化由神经元活动驱动。
NPJ Parkinsons Dis. 2023 Jan 16;9(1):4. doi: 10.1038/s41531-023-00444-w.
8
Plasma and CSF biomarkers in a memory clinic: Head-to-head comparison of phosphorylated tau immunoassays.在记忆诊所中进行的血浆和脑脊液生物标志物检测：磷酸化tau 免疫分析的头对头比较。
Alzheimers Dement. 2023 May;19(5):1913-1924. doi: 10.1002/alz.12841. Epub 2022 Nov 12.
9
An ultra-sensitive immunoassay detects and quantifies soluble Aβ oligomers in human plasma.一种超敏免疫分析检测和定量人血浆中的可溶性 Aβ 寡聚物。
Alzheimers Dement. 2022 Jun;18(6):1186-1202. doi: 10.1002/alz.12457. Epub 2021 Sep 22.
10
Stem cell-derived neurons reflect features of protein networks, neuropathology, and cognitive outcome of their aged human donors.干细胞衍生的神经元反映了其年老供体的蛋白质网络、神经病理学和认知结果的特征。
Neuron. 2021 Nov 3;109(21):3402-3420.e9. doi: 10.1016/j.neuron.2021.08.003. Epub 2021 Sep 1.