Synaptosomal-Associated Protein 25 kDA (SNAP-25) Levels in Cerebrospinal Fluid: Implications for Alzheimer's Disease Diagnosis and Monitoring.

IF 1.6 4区 医学 Q4 NEUROSCIENCES
Synapse Pub Date : 2025-03-01 DOI:10.1002/syn.70010
Sofia Hjorth Wolner, Helena Sophia Gleerup, Christian Sandøe Musaeus, Peter Høgh, Nicholas J Ashton, Ann Brinkmalm, Johanna Nilsson, Lana Grötschel, Henrik Zetterberg, Kaj Blennow, Steen Gregers Hasselbalch, Anne Byriel Walls, Anja Hviid Simonsen
{"title":"Synaptosomal-Associated Protein 25 kDA (SNAP-25) Levels in Cerebrospinal Fluid: Implications for Alzheimer's Disease Diagnosis and Monitoring.","authors":"Sofia Hjorth Wolner, Helena Sophia Gleerup, Christian Sandøe Musaeus, Peter Høgh, Nicholas J Ashton, Ann Brinkmalm, Johanna Nilsson, Lana Grötschel, Henrik Zetterberg, Kaj Blennow, Steen Gregers Hasselbalch, Anne Byriel Walls, Anja Hviid Simonsen","doi":"10.1002/syn.70010","DOIUrl":null,"url":null,"abstract":"<p><p>Synaptic degeneration has been linked to cognitive decline. The presynaptic protein, synaptosomal-associated protein 25 kDA (SNAP-25), is crucial for synaptic transmission and has been suggested as a biomarker in Alzheimer's disease (AD). In the current study, we investigated the ability of SNAP-25 to differentiate between heterogenous dementia etiologies and whether SNAP-25 could be a staging marker in AD. SNAP-25 in the cerebrospinal fluid (CSF) from a retrospective (n = 187) and a prospective (n = 134) cohort was investigated with immunoprecipitation mass spectrometry (IP-MS) and single-molecule array (Simoa), respectively. Both cohorts consisted of healthy controls (HC) and patients with cognitive decline of different etiologies. CSF SNAP-25 concentration was higher in AD and non-neurodegenerative diseases (i.e., vascular dementia) compared with controls but did not differ between AD and non-AD neurodegenerative diseases. We found a trend toward an association between SNAP-25 and disease burden when comparing HC, mild cognitive impairment due to AD, and AD. CSF SNAP-25 concentrations were strongly associated with CSF phosphorylated tau (p-tau) concentrations, thus strengthening the link between synaptic dysfunction and tau pathophysiology in AD. Our initial findings suggest that SNAP-25 may be a potential biomarker for differentiating AD from dementia due to other etiologies. However, due to the significant association between SNAP-25 and p-tau proteins, the clinical utility of SNAP-25 as a diagnostic biomarker for AD may be limited, while SNAP-25 may be useful for monitoring disease progression or treatment response.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 2","pages":"e70010"},"PeriodicalIF":1.6000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11800177/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Synapse","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/syn.70010","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0

Abstract

Synaptic degeneration has been linked to cognitive decline. The presynaptic protein, synaptosomal-associated protein 25 kDA (SNAP-25), is crucial for synaptic transmission and has been suggested as a biomarker in Alzheimer's disease (AD). In the current study, we investigated the ability of SNAP-25 to differentiate between heterogenous dementia etiologies and whether SNAP-25 could be a staging marker in AD. SNAP-25 in the cerebrospinal fluid (CSF) from a retrospective (n = 187) and a prospective (n = 134) cohort was investigated with immunoprecipitation mass spectrometry (IP-MS) and single-molecule array (Simoa), respectively. Both cohorts consisted of healthy controls (HC) and patients with cognitive decline of different etiologies. CSF SNAP-25 concentration was higher in AD and non-neurodegenerative diseases (i.e., vascular dementia) compared with controls but did not differ between AD and non-AD neurodegenerative diseases. We found a trend toward an association between SNAP-25 and disease burden when comparing HC, mild cognitive impairment due to AD, and AD. CSF SNAP-25 concentrations were strongly associated with CSF phosphorylated tau (p-tau) concentrations, thus strengthening the link between synaptic dysfunction and tau pathophysiology in AD. Our initial findings suggest that SNAP-25 may be a potential biomarker for differentiating AD from dementia due to other etiologies. However, due to the significant association between SNAP-25 and p-tau proteins, the clinical utility of SNAP-25 as a diagnostic biomarker for AD may be limited, while SNAP-25 may be useful for monitoring disease progression or treatment response.

脑脊液中突触体相关蛋白25kda (SNAP-25)水平:对阿尔茨海默病诊断和监测的意义
突触退化与认知能力下降有关。突触前蛋白,突触体相关蛋白25 kDA (SNAP-25),对突触传递至关重要,已被认为是阿尔茨海默病(AD)的生物标志物。在目前的研究中,我们研究了SNAP-25区分异质性痴呆病因的能力,以及SNAP-25是否可以作为AD的分期标志。采用免疫沉淀质谱(IP-MS)和单分子阵列(Simoa)分别对回顾性(n = 187)和前瞻性(n = 134)队列的脑脊液(CSF)中的SNAP-25进行了研究。两个队列均由健康对照(HC)和不同病因的认知衰退患者组成。与对照组相比,脑脊液SNAP-25浓度在AD和非神经退行性疾病(即血管性痴呆)中较高,但在AD和非AD神经退行性疾病之间没有差异。在比较HC、AD引起的轻度认知障碍和AD时,我们发现SNAP-25与疾病负担之间存在关联的趋势。脑脊液SNAP-25浓度与脑脊液磷酸化tau (p-tau)浓度密切相关,从而加强了AD中突触功能障碍与tau病理生理之间的联系。我们的初步研究结果表明,SNAP-25可能是区分AD与其他病因导致的痴呆的潜在生物标志物。然而,由于SNAP-25和p-tau蛋白之间的显著关联,SNAP-25作为AD诊断生物标志物的临床应用可能有限,而SNAP-25可能用于监测疾病进展或治疗反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Synapse
Synapse 医学-神经科学
CiteScore
3.80
自引率
0.00%
发文量
38
审稿时长
4-8 weeks
期刊介绍: SYNAPSE publishes articles concerned with all aspects of synaptic structure and function. This includes neurotransmitters, neuropeptides, neuromodulators, receptors, gap junctions, metabolism, plasticity, circuitry, mathematical modeling, ion channels, patch recording, single unit recording, development, behavior, pathology, toxicology, etc.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信