Cerebrospinal fluid α-synuclein seed amplification assay positivity is associated with increased plasma neurofilament light chain in Alzheimer's disease

IF 6 2区医学 Q1 NEUROSCIENCES

Neurobiology of Disease Pub Date : 2026-01-01 Epub Date: 2025-12-22 DOI:10.1016/j.nbd.2025.107234

Giovanni Bellomo PhD , Andrea Toja MD , Lorenzo Gaetani MD, PhD , Giovanna Nardi MD , Federico Paolini Paoletti MD, PhD , Davide Chiasserini PhD , Lucilla Parnetti MD, PhD

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引用次数: 0

Abstract

Background

Synucleinopathy is the most common co-pathology in Alzheimer's disease (AD) and can be detected in vivo using cerebrospinal fluid (CSF) alpha-synuclein seed amplification assays (synSAA). CSF synSAA positivity has been linked to worse clinical outcome. This study investigated whether synSAA positivity is also associated with levels of plasma neurofilament light chain (NfL), a sensitive, unspecific marker of neurodegeneration.

Methods

We retrospectively analyzed a cohort of 240 individuals across the AD clinical continuum who had undergone clinical, neuropsychological, and biomarker assessments including CSF synSAA. Analyses involving plasma NfL were conducted in the subgroup with available plasma samples collected at the time of lumbar puncture (n = 166). One-way and two-way ANOVA were used to compare log-transformed NfL levels among AD stages, according to synSAA status. Logistic regression models examined associations between log-transformed NfL and synSAA status, adjusting for age and AD stage.

Findings

No significant age difference was found between synSAA-positive and negative groups. Plasma NfL levels were significantly higher in synSAA-positive individuals. This association remained significant after adjusting for age and AD clinical stage.

Interpretation

In AD patients, CSF synSAA positivity is associated with increase of plasma NfL levels along the AD clinical continuum. This finding supports the knowledge that synuclein co-pathology represents a contributive factor of neurodegeneration in AD patients.

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脑脊液α-突触核蛋白种子扩增试验阳性与阿尔茨海默病血浆神经丝轻链增高相关。

背景：突触核蛋白病是阿尔茨海默病（AD）中最常见的共同病理，可以通过脑脊液(CSF) α -突触核蛋白种子扩增试验（synSAA）在体内检测到。CSF synSAA阳性与较差的临床结果有关。这项研究调查了synSAA阳性是否也与血浆神经丝轻链（NfL）水平有关，NfL是一种敏感的、非特异性的神经变性标志物。方法：我们回顾性分析了240名阿尔茨海默病临床连续体患者，他们接受了临床、神经心理学和生物标志物评估，包括CSF synSAA。在腰椎穿刺时收集血浆样本的亚组中进行血浆NfL分析（n = 166）。根据synSAA状态，采用单因素和双因素方差分析比较不同AD阶段的对数转换NfL水平。逻辑回归模型检验了对数转换后的NfL与synSAA状态之间的关系，并对年龄和AD分期进行了调整。结果：synsaa阳性组与阴性组无明显年龄差异。血浆NfL水平在synsaa阳性个体中显著升高。在调整了年龄和阿尔茨海默病的临床分期后，这种关联仍然显著。解释：在AD患者中，CSF synSAA阳性与AD临床连续体中血浆NfL水平升高相关。这一发现支持了突触核蛋白共病理是阿尔茨海默病患者神经退行性变的一个促进因素的认识。

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

Neurobiology of Disease 医学-神经科学

CiteScore

11.20

自引率

3.30%

发文量

270

审稿时长

76 days

期刊介绍： Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.