前驱期至中度阿尔茨海默病患者的脑脊液补体蛋白会升高，而抗 tau 抗体 semorinemab 不会改变这种情况。

IF 13 1区医学 Q1 CLINICAL NEUROLOGY Alzheimer's & Dementia Pub Date : 2024-10-06 DOI:10.1002/alz.14271

Cosme Sandoval, Julie Lee, Balazs Toth, Rajini Nagaraj, Stephen P. Schauer, Jennifer Hoffman, Emilia Calderon, Gwendlyn Kollmorgen, Sandra M. Sanabria Bohórquez, Cecilia Monteiro, Edmond Teng, Jesse E. Hanson, Felix L. Yeh, Johnny Gutierrez, Anne Biever

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引用次数: 0

摘要

简介：越来越多的证据表明神经炎症在阿尔茨海默病（AD）中的作用：越来越多的证据表明神经炎症在阿尔茨海默病（AD）中的作用。我们研究了AD患者脑脊液（CSF）中的补体途径活性，并评估了抗tau抗体semorinemab对其的调节作用：方法：采用免疫测定法测定AD患者脑脊液补体蛋白C4、B因子（FB）、C3及其裂解片段C4a、C3a和Bb因子（Bb）：所有测定的CSF补体蛋白在AD与CU受试者中均有所增加，其中C4a的增加最为明显。最后，semorinemab对CSF补体蛋白没有明显的药效学影响：讨论：CSF C4a、C4、C3a、C3、Bb和FB水平的升高与AD大脑中的补体激活一致。尽管CSF中可溶性tau物种有所减少，但semorinemab并不影响补体蛋白水平或活性。要确定补体蛋白作为AD神经炎症生物标志物的价值，还需要进一步的研究：脑脊液（CSF）补体蛋白C4a、C3a、Bb、C4、C3和B因子水平在阿尔茨海默病（AD）患者中较认知功能未受损（CU）患者队列中有所增加。基线 CSF 补体蛋白水平与阿尔茨海默病患者的神经轴变性和神经胶质活化生物标记物相关。与安慰剂组相比，研究性抗tau抗体semorinemab不会影响CSF补体蛋白水平或活性。

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CSF complement proteins are elevated in prodromal to moderate Alzheimer's disease patients and are not altered by the anti-tau antibody semorinemab

INTRODUCTION

Growing evidence suggests a role for neuroinflammation in Alzheimer's disease (AD). We investigated complement pathway activity in AD patient cerebrospinal fluid (CSF) and evaluated its modulation by the anti-tau antibody semorinemab.

METHODS

Immunoassays were applied to measure CSF complement proteins C4, factor B (FB), C3 and their cleavage fragments C4a, C3a, and factor Bb (Bb) in AD patients and a separate cognitively unimpaired (CU) cohort.

RESULTS

All measured CSF complement proteins were increased in AD versus CU subjects, with C4a displaying the most robust increase. Finally, semorinemab did not have a significant pharmacodynamic effect on CSF complement proteins.

DISCUSSION

Elevated levels of CSF C4a, C4, C3a, C3, Bb, and FB are consistent with complement activation in AD brains. Despite showing a reduction in CSF soluble tau species, semorinemab did not impact complement protein levels or activity. Further studies are needed to determine the value of complement proteins as neuroinflammation biomarkers in AD.

Highlights

Cerebrospinal fluid (CSF) complement proteins C4a, C3a, Bb, C4, C3, and factor B levels were increased in Alzheimer's disease (AD) patients compared to a separate cognitively unimpaired (CU) cohort.
Baseline CSF complement protein levels were correlated with neuro-axonal degeneration and glial activation biomarkers in AD patients.
The investigational anti-tau antibody semorinemab did not impact CSF complement protein levels or activity relative to the placebo arm.

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.