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Aβ诱导的膜序改变的荧光寿命成像-相量分析(FLIM-ϕ):迈向基于细胞的早期阿尔茨海默病诊断生物传感器

FLIM-Phasor Analysis (FLIM-ϕ) of Aβ-Induced Membrane Order Alterations: Towards a Cell-Based Biosensor for Early Alzheimer's Disease Diagnosis.

作者信息

Battisti Antonella, Ortore Maria Grazia, Vilasi Silvia, Sgarbossa Antonella

机构信息

NEST, Nanoscience Institute-CNR and Scuola Normale Superiore, p.zza San Silvestro 12, I-56127 Pisa, Italy.

Biophysics Institute-CNR, Via Ugo La Malfa 153, I-90146 Palermo, Italy.

出版信息

Micromachines (Basel). 2025 Feb 19;16(2):234. doi: 10.3390/mi16020234.

DOI:10.3390/mi16020234
PMID:40047700
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11857758/
Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, and its early detection can be critical for a prompt intervention that can potentially slow down the disease progression and improve the patient's quality of life. However, a diagnosis based solely on clinical symptoms can be challenging, especially in the early stages, while the detection of specific biomarkers such as amyloid-β peptide (Aβ) and tau proteins can provide objective evidence for diagnosis. In this work, we explored the effects of Aβ peptide on cell membrane properties thanks to fluorescence lifetime imaging (FLIM) combined with the phasor analysis (FLIM-ϕ). The results showed that the membrane viscosity is altered by the presence of Aβ peptide and that cells experience this effect even at nanomolar concentrations of peptide. This considerable sensitivity opens up the possibility of envisioning a cell-based biosensor able to detect very low concentrations of Aβ in a biological fluid, thus enabling timely diagnosis and intervention.

摘要

阿尔茨海默病(AD)是一种进行性神经退行性疾病,其早期检测对于及时干预至关重要,这种干预可能会减缓疾病进展并提高患者的生活质量。然而,仅基于临床症状进行诊断可能具有挑战性,尤其是在疾病早期,而检测特定生物标志物,如淀粉样β肽(Aβ)和tau蛋白,可以为诊断提供客观证据。在这项工作中,我们借助荧光寿命成像(FLIM)结合相量分析(FLIM-ϕ),探索了Aβ肽对细胞膜特性的影响。结果表明,Aβ肽的存在会改变膜粘度,并且即使在纳摩尔浓度的肽环境下,细胞也会受到这种影响。这种相当高的灵敏度为设想一种基于细胞的生物传感器开辟了可能性,该传感器能够检测生物流体中极低浓度的Aβ,从而实现及时诊断和干预。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bd/11857758/a3871928c150/micromachines-16-00234-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bd/11857758/c7b6ae0ca0d0/micromachines-16-00234-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bd/11857758/a3871928c150/micromachines-16-00234-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bd/11857758/c7b6ae0ca0d0/micromachines-16-00234-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bd/11857758/a3871928c150/micromachines-16-00234-g002.jpg

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本文引用的文献

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Advances in Blood Biomarkers for Alzheimer's Disease: Ultra-Sensitive Detection Technologies and Impact on Clinical Diagnosis.阿尔茨海默病血液生物标志物的进展:超灵敏检测技术及其对临床诊断的影响
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Label-free detection of Aβ-42: a liquid crystal droplet approach for Alzheimer's disease diagnosis.
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Alzheimer's Disease Biomarker Analysis Using Targeted Mass Spectrometry.采用靶向质谱分析法对阿尔茨海默病的生物标志物进行分析。
Mol Cell Proteomics. 2024 Feb;23(2):100721. doi: 10.1016/j.mcpro.2024.100721. Epub 2024 Jan 20.
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Smart electrochemical sensing of amyloid-beta to manage total Alzheimer's diseases.用于管理阿尔茨海默病整体状况的淀粉样β蛋白智能电化学传感
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Research Progress on Multifunctional Fluorescent Probes for Biological Imaging, Food and Environmental Detection.生物成像、食品和环境检测用多功能荧光探针的研究进展。
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Amyloid β interaction with model cell membranes - What are the toxicity-defining properties of amyloid β?淀粉样β与模型细胞膜的相互作用——淀粉样β的毒性定义特性是什么?
Int J Biol Macromol. 2022 Mar 1;200:520-531. doi: 10.1016/j.ijbiomac.2022.01.117. Epub 2022 Jan 21.
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Blood-based biomarkers for Alzheimer's disease.用于阿尔茨海默病的基于血液的生物标志物。
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