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, Melina Helfrich, Marcus Höring, Frederik Großerüschkamp, Gerhard Liebisch, 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.
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.