脂褐素自身荧光混淆了老年小鼠大脑中细胞内淀粉样蛋白β的检测。

IF 2.7 Q3 CLINICAL NEUROLOGY
Aging brain Pub Date : 2025-08-08 eCollection Date: 2025-01-01 DOI:10.1016/j.nbas.2025.100148
Godfried Dougnon, Hideaki Matsui
{"title":"脂褐素自身荧光混淆了老年小鼠大脑中细胞内淀粉样蛋白β的检测。","authors":"Godfried Dougnon, Hideaki Matsui","doi":"10.1016/j.nbas.2025.100148","DOIUrl":null,"url":null,"abstract":"<p><p>Intracellular amyloid β (Aβ) accumulation is a contentious feature of Alzheimer's disease (AD), increasingly reported in young adults and aged animal models of AD. However, autofluorescent lipofuscin granules which consist of a mixture of highly oxidized lipids, misfolded proteins, and metals, accumulates with aging in neurons and microglia and renders difficult the interpretation of immunofluorescence-based studies. Here, we show that lipofuscin accumulation in aged wild-type (WT) mouse brains exhibits significant spectral overlap with commonly used antibodies for Aβ detection, leading to potential misinterpretation of intracellular Aβ signals. Through a combination of dye staining, immunohistochemistry (IHC), and confocal microscopy, we show that fluorescence signals resembling intracellular Aβ and commonly reported in aged animal models of AD, may reflect the presence of lipofuscin granules. Importantly, these signals persisted in control sections where primary Aβ antibodies were omitted, but disappeared following TrueBlack autofluorescence quencher. We also performed Aβ immunofluorescence staining using 5xFAD mice as model for AD, revealing that intracellular Aβ in these models can be diminished by TrueBlack treatment, thus confounding the interpretation of true intracellular Aβ signals. Our findings underscore the need for caution in interpreting intracellular Aβ signals in young adults and aged models of Aβ pathology inside neurons or microglia.</p>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":"8 ","pages":"100148"},"PeriodicalIF":2.7000,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356383/pdf/","citationCount":"0","resultStr":"{\"title\":\"Lipofuscin autofluorescence confounds intracellular amyloid β detection in the aged mouse brain.\",\"authors\":\"Godfried Dougnon, Hideaki Matsui\",\"doi\":\"10.1016/j.nbas.2025.100148\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Intracellular amyloid β (Aβ) accumulation is a contentious feature of Alzheimer's disease (AD), increasingly reported in young adults and aged animal models of AD. However, autofluorescent lipofuscin granules which consist of a mixture of highly oxidized lipids, misfolded proteins, and metals, accumulates with aging in neurons and microglia and renders difficult the interpretation of immunofluorescence-based studies. Here, we show that lipofuscin accumulation in aged wild-type (WT) mouse brains exhibits significant spectral overlap with commonly used antibodies for Aβ detection, leading to potential misinterpretation of intracellular Aβ signals. Through a combination of dye staining, immunohistochemistry (IHC), and confocal microscopy, we show that fluorescence signals resembling intracellular Aβ and commonly reported in aged animal models of AD, may reflect the presence of lipofuscin granules. Importantly, these signals persisted in control sections where primary Aβ antibodies were omitted, but disappeared following TrueBlack autofluorescence quencher. We also performed Aβ immunofluorescence staining using 5xFAD mice as model for AD, revealing that intracellular Aβ in these models can be diminished by TrueBlack treatment, thus confounding the interpretation of true intracellular Aβ signals. Our findings underscore the need for caution in interpreting intracellular Aβ signals in young adults and aged models of Aβ pathology inside neurons or microglia.</p>\",\"PeriodicalId\":72131,\"journal\":{\"name\":\"Aging brain\",\"volume\":\"8 \",\"pages\":\"100148\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2025-08-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356383/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Aging brain\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.nbas.2025.100148\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Aging brain","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.nbas.2025.100148","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

摘要

细胞内β淀粉样蛋白(a β)积累是阿尔茨海默病(AD)的一个有争议的特征,越来越多地在年轻成人和老年AD动物模型中报道。然而,由高度氧化的脂质、错误折叠的蛋白质和金属的混合物组成的自荧光脂褐素颗粒,随着神经元和小胶质细胞的衰老而积累,使得基于免疫荧光的研究难以解释。在这里,我们发现脂褐素在衰老野生型(WT)小鼠大脑中的积累与常用的Aβ检测抗体表现出显著的光谱重叠,导致细胞内Aβ信号的潜在误解。通过染料染色、免疫组织化学(IHC)和共聚焦显微镜的结合,我们发现类似于细胞内a β的荧光信号,通常在老年AD动物模型中报道,可能反映了脂褐素颗粒的存在。重要的是,这些信号在省略一抗Aβ抗体的对照切片中持续存在,但在TrueBlack自身荧光淬灭剂后消失。我们还使用5xFAD小鼠作为AD模型进行了Aβ免疫荧光染色,发现TrueBlack处理可以减少这些模型中的细胞内Aβ,从而混淆了对细胞内真实Aβ信号的解释。我们的研究结果强调了在解释年轻成人和老年神经元或小胶质细胞内的Aβ病理模型的细胞内Aβ信号时需要谨慎。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Lipofuscin autofluorescence confounds intracellular amyloid β detection in the aged mouse brain.

Intracellular amyloid β (Aβ) accumulation is a contentious feature of Alzheimer's disease (AD), increasingly reported in young adults and aged animal models of AD. However, autofluorescent lipofuscin granules which consist of a mixture of highly oxidized lipids, misfolded proteins, and metals, accumulates with aging in neurons and microglia and renders difficult the interpretation of immunofluorescence-based studies. Here, we show that lipofuscin accumulation in aged wild-type (WT) mouse brains exhibits significant spectral overlap with commonly used antibodies for Aβ detection, leading to potential misinterpretation of intracellular Aβ signals. Through a combination of dye staining, immunohistochemistry (IHC), and confocal microscopy, we show that fluorescence signals resembling intracellular Aβ and commonly reported in aged animal models of AD, may reflect the presence of lipofuscin granules. Importantly, these signals persisted in control sections where primary Aβ antibodies were omitted, but disappeared following TrueBlack autofluorescence quencher. We also performed Aβ immunofluorescence staining using 5xFAD mice as model for AD, revealing that intracellular Aβ in these models can be diminished by TrueBlack treatment, thus confounding the interpretation of true intracellular Aβ signals. Our findings underscore the need for caution in interpreting intracellular Aβ signals in young adults and aged models of Aβ pathology inside neurons or microglia.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Aging brain
Aging brain Neuroscience (General), Geriatrics and Gerontology
自引率
0.00%
发文量
0
×
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:604180095
Book学术官方微信