Conference Papers Year : 2023

Detection of Aβ 1-42 aggregates by RT-FAST: Toward a new tool for the diagnostic of Alzheimer's disease

Abstract

Self-assembly of the misfolded Ab 1-42 peptide is involved in Alzheimer’s dis- ease (AD). The oligomeric species formed at an early stage of aggregation are considered as one of the main biomarkers. Nowadays, no tools are available to detect them due to their transient nature and their low concentration (fM) in biofluids such as the cerebro-spinal fluid (CSF). Therefore, our purpose is to propose an approach to detect these species directly in the CSF. Recently, we developed an innovative method to detect preformed a-synuclein oligomers called Real-Time Fast Amyloid Seeding and Translocation (RT-FAST)[1]. The principle is based on the properties of preformed oligomers to promote the aggregation of monomers providing large aggregates faster than the control condition (without oligomers). These newly formed aggregates are detected using a single nanopore by resistive pulse sensing. The latter consists to measure transient ionic current blockages caused by the passage of an aggregate. In this approach, we use a nanopipette as vial to accelerate aggregation (reservoir about 70 mL) and nanopore sensors. Experimentally, current blockades are observed after 120 minutes of aggregation only for the sample containing preformed Ab 1-42 oligomers in buffer. Further analysis of the current blockade amplitudes allows estimating an aggregate volume in the order of 105 nm3 using a geometrical model. Interestingly, in presence of CSF same trend is observed. However, blockades are detected after 240 minutes of aggregation. One possible explanation could be that the molecules present in CSF slow down aggregation. In addition, CSF proteins decrease the adsorption constant of the Ab known to accelerate aggregation.

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Dates and versions

hal-04941082 , version 1 (11-02-2025)

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Cite

Nathan Meyer, Jean-Marc Janot, Joan Torrent, Sébastien Balme. Detection of Aβ 1-42 aggregates by RT-FAST: Toward a new tool for the diagnostic of Alzheimer's disease. Biophysical Society 67th Annual Meeting (BPS 2023), Biophysical Society, Feb 2023, San Diego (CA), United States. pp.456a / 2217-Plat, ⟨10.1016/j.bpj.2022.11.2453⟩. ⟨hal-04941082⟩
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