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. 2024 Oct 8;13(1):51.
doi: 10.1186/s40035-024-00444-7.

Ultrasensitive detection of TDP-43 and amyloid-β protein aggregates using micelle-assisted seed amplification assay

Sora Sakamoto  1 , Yuichi Riku  2   3 , Teiko Komori Nomura  4 , Akio Kimura  5 , Naoki Yamahara  5 , Kazuki Ohuchi  1 , Mari Yoshida  2 , Yasushi Iwasaki  2 , Takayoshi Shimohata  5   6 , Masatoshi Inden  1 , Ryo Honda  7   8
Affiliations

Ultrasensitive detection of TDP-43 and amyloid-β protein aggregates using micelle-assisted seed amplification assay

Sora Sakamoto et al. Transl Neurodegener. .
No abstract available

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Conflict of interest statement

R.H., M.I., and Y.S. are the authors of a pending patent on the mSAA developed in this study. The other authors declare no potential conflicts of interest.

Figures

Fig. 1
Fig. 1
a Screening result of surfactants at the concentration of 0.1% unless otherwise noted. b Performance of the enhanced TDP-43 SAA. The left panel shows the time courses of ThT fluorescence at different seed concentrations. The right panel presents tlag values derived from the left panel (mean ± SE, *P < 0.05, **P < 0.005, unpaired two-tailed t-test compared to no seed). c Outline of the experiment using FTLD-TDP patients’ brains. Small sections from the frontal and temporal lobes of frozen brains in the right hemisphere were sampled and subjected to SAA, immunoblotting, and IHC. d The tlag values of the patient-derived brain homogenates obtained at a 1:250 dilution ratio (*P < 0.05, **P < 0.005, Dunnett’s test compared to control brain homogenate). Frontal lobes from the TDP#1 and #2 patients were evaluated in two different extracts. e, f Bubble plots showing the correlation of SAA with immunoblot and IHC scores. The size of the bubbles is proportional to their frequency. g Left panel: SPR sensorgrams of Brij-58 binding to TDP-43 monomers. Right panel: a dose–response curve derived from the left panel. h Correlation between ∆tlag and Kd values of 21 surfactants. i SEC profiles of 20 µM TDP-43 monomers mixed with Brij-58 prior to analysis. j Schematic of how Brij-58 redirects aggregation-prone protein monomers to the seed amplification pathway. k SPR sensorgrams of Brij-58 binding to Aβ monomers. l Time courses of ThT fluorescence of Aβ SAA (with 1.5 M urea) at different seed concentrations, both without and with 0.1% Brij-58
See this image and copyright information in PMC

References

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