Unsaturated Fatty Acids Are Decreased in Aβ Plaques in Alzheimer's Disease

IF 4.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Neurochemistry Pub Date : 2025-01-18 DOI:10.1111/jnc.16306
Dominik Röhr, Melina Helfrich, Marcus Höring, Frederik Großerüschkamp, Gerhard Liebisch, Klaus Gerwert
{"title":"Unsaturated Fatty Acids Are Decreased in Aβ Plaques in Alzheimer's Disease","authors":"Dominik Röhr,&nbsp;Melina Helfrich,&nbsp;Marcus Höring,&nbsp;Frederik Großerüschkamp,&nbsp;Gerhard Liebisch,&nbsp;Klaus Gerwert","doi":"10.1111/jnc.16306","DOIUrl":null,"url":null,"abstract":"<p>Alzheimer's disease (AD) is characterized by the accumulation of amyloid-beta (Aβ) plaques in the brain, contributing to neurodegeneration. This study investigates lipid alterations within these plaques using a novel, label-free, multimodal approach. Combining infrared (IR) imaging, machine learning, laser microdissection (LMD), and flow injection analysis mass spectrometry (FIA-MS), we provide the first comprehensive lipidomic analysis of chemically unaltered Aβ plaques in post-mortem human AD brain tissue. IR imaging revealed decreased lipid unsaturation within plaques, evidenced by a reduction in the alkene (=C-H) stretching vibration band. The high spatial resolution of IR imaging, coupled with machine learning-based plaque detection, enabled precise and label-free extraction of plaques via LMD. Subsequent FIA-MS analysis confirmed a significant increase in short-chain saturated lipids and a concomitant decrease in long-chain unsaturated lipids within plaques compared to the surrounding tissue. These findings highlight a substantial depletion of unsaturated fatty acids (UFAs) in Aβ plaques, suggesting a pivotal role for lipid dysregulation and oxidative stress in AD pathology. This study advances our understanding of the molecular landscape of Aβ plaques and underscores the potential of lipid-based therapeutic strategies in AD.\n <figure>\n <div><picture>\n <source></source></picture><p></p>\n </div>\n </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 1","pages":""},"PeriodicalIF":4.2000,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742699/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neurochemistry","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/jnc.16306","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-beta (Aβ) plaques in the brain, contributing to neurodegeneration. This study investigates lipid alterations within these plaques using a novel, label-free, multimodal approach. Combining infrared (IR) imaging, machine learning, laser microdissection (LMD), and flow injection analysis mass spectrometry (FIA-MS), we provide the first comprehensive lipidomic analysis of chemically unaltered Aβ plaques in post-mortem human AD brain tissue. IR imaging revealed decreased lipid unsaturation within plaques, evidenced by a reduction in the alkene (=C-H) stretching vibration band. The high spatial resolution of IR imaging, coupled with machine learning-based plaque detection, enabled precise and label-free extraction of plaques via LMD. Subsequent FIA-MS analysis confirmed a significant increase in short-chain saturated lipids and a concomitant decrease in long-chain unsaturated lipids within plaques compared to the surrounding tissue. These findings highlight a substantial depletion of unsaturated fatty acids (UFAs) in Aβ plaques, suggesting a pivotal role for lipid dysregulation and oxidative stress in AD pathology. This study advances our understanding of the molecular landscape of Aβ plaques and underscores the potential of lipid-based therapeutic strategies in AD.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
不饱和脂肪酸在阿尔茨海默病的β斑块中减少。
阿尔茨海默病(AD)的特点是大脑中淀粉样蛋白(Aβ)斑块的积累,导致神经变性。本研究使用一种新颖的、无标签的、多模式的方法来研究这些斑块内的脂质改变。结合红外(IR)成像、机器学习、激光显微解剖(LMD)和流动注射分析质谱(FIA-MS),我们首次对死后人类AD脑组织中化学未改变的Aβ斑块进行了全面的脂质组学分析。红外成像显示斑块内脂质不饱和度降低,烯烃(=C-H)拉伸振动带减少。红外成像的高空间分辨率,加上基于机器学习的斑块检测,使得通过LMD精确和无标签地提取斑块成为可能。随后的FIA-MS分析证实,与周围组织相比,斑块内短链饱和脂质显著增加,同时长链不饱和脂质减少。这些发现强调了a β斑块中不饱和脂肪酸(UFAs)的大量消耗,表明脂质失调和氧化应激在AD病理中起关键作用。这项研究促进了我们对β斑块分子格局的理解,并强调了基于脂质治疗AD策略的潜力。
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 去求助
来源期刊
Journal of Neurochemistry
Journal of Neurochemistry 医学-神经科学
CiteScore
9.30
自引率
2.10%
发文量
181
审稿时长
2.2 months
期刊介绍: Journal of Neurochemistry focuses on molecular, cellular and biochemical aspects of the nervous system, the pathogenesis of neurological disorders and the development of disease specific biomarkers. It is devoted to the prompt publication of original findings of the highest scientific priority and value that provide novel mechanistic insights, represent a clear advance over previous studies and have the potential to generate exciting future research.
期刊最新文献
Correction to “Inhalation of Hydrogen Gas Mitigates Sevoflurane-Induced Neuronal Apoptosis in the Neonatal Cortex and is Associated With Changes in Protein Phosphorylation” Longitudinal Investigation of Brain and Spinal Cord Pericytes After Inducible PDGFRβ+ Cell Ablation in Adult Mice The Glutamate/GABA-Glutamine Cycle: Insights, Updates, and Advances Proteolysis-Based Biomarker Repertoire of the Neurofilament Proteome Surgical Stress and Non-Surgery Related Stress Synergistically Trigger Meningeal CD8+ T Cells Accumulation and Subsequent Brain Dysfunction in Mice
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1