Associations between fluid biomarkers and PET imaging ([11C]UCB-J) of synaptic pathology in Alzheimer's disease

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-07-10 DOI:10.1002/alz.70403

Johanna Nilsson, Adam P. Mecca, Nicholas J. Ashton, Elaheh Salardini, Ryan S. O'Dell, Richard E. Carson, Andrea L. Benedet, Kaj Blennow, Henrik Zetterberg, Christopher H. van Dyck, Ann Brinkmalm

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Abstract

INTRODUCTION

Positron emission tomography (PET) imaging with ligands for synaptic vesicle glycoprotein 2A (SV2A) has emerged as a promising methodology for measuring synaptic density in Alzheimer's disease (AD). We investigated the relationship between SV2A PET and CSF synaptic protein changes of AD patients.

METHOD

Twenty-one participants with early AD and seven cognitively normal (CN) individuals underwent [¹¹C]UCB-J PET. We used mass spectrometry to measure a panel of synaptic proteins in cerebrospinal fluid (CSF).

RESULTS

In the AD group, higher levels of syntaxin-7 and PEBP-1 were associated with lower global synaptic density. In the total sample, lower global synaptic density was associated with higher levels of AP2B1, neurogranin, γ-synuclein, GDI-1, PEBP-1, syntaxin-1B, and syntaxin-7 but not with the levels of the neuronal pentraxins or 14-3-3 zeta/delta.

CONCLUSION

Reductions of synaptic density found in AD compared to CN participants using [¹¹C]UCB-J PET were observed to be associated with CSF biomarker levels of synaptic proteins.

Highlights

A panel of synaptic proteins was quantified in the CSF using mass spectrometry.
SV2A ([¹¹C]UCB-J) PET was used to quantify synaptic density.
Reductions of synaptic density were associated with CSF synaptic biomarker levels.

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阿尔茨海默病突触病理的液体生物标志物与PET成像（[11C]UCB-J）的相关性

使用突触囊泡糖蛋白2A （SV2A）配体的正电子发射断层扫描（PET）成像已成为测量阿尔茨海默病（AD）突触密度的一种很有前途的方法。我们研究了SV2A PET与AD患者脑脊液突触蛋白变化的关系。方法21例早期AD患者和7例认知正常（CN）患者接受[11C]UCB-J PET检查。我们使用质谱法测量脑脊液（CSF）中的一组突触蛋白。结果在AD组中，较高水平的syntaxin-7和PEBP-1与较低的整体突触密度相关。在总样本中，较低的整体突触密度与较高的AP2B1、神经粒蛋白、γ-突触核蛋白、GDI-1、PEBP-1、syntaxin-1B和syntaxin-7水平相关，但与神经元戊烷素或14-3-3 zeta/delta水平无关。结论：使用[11C]UCB-J PET观察，AD患者突触密度较CN患者降低，与脑脊液突触蛋白生物标志物水平相关。使用质谱法对脑脊液中的突触蛋白进行定量分析。采用SV2A ([11C]UCB-J) PET定量测定突触密度。突触密度降低与脑脊液突触生物标志物水平相关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.