| 研究実績の概要 |
On-chip detection successfully demonstrated differences between MTs exposed to different concentrations of tau protein. Higher tau concentration resulted in a denser attachment on MTs causing higher decrease in the average velocity compared to lower concentration showing smaller decrease with respect to the no-tau control experiments. Also, effect of different tau isoforms were detected: (i) Tau with higher MT-binding repeats (MTBR) caused slower bead motion compared to tau with lower MTBR, (ii) Tau with shorter projection domain (PD) caused slower bead motion compared to tau with longer PD.
A novel technique for mutated tau detection was introduced. As mutated tau has limited attachment to MTs, detection is extremely difficult. Thus, an additional pre-incubation step was added to mix healthy and mutated tau proteins for 8 hours. Mutated tau can affect the healthy tau and decrease the healthy tau concentration in the solution that will later be used in the detection method. The results showed that having the same healthy tau concentration with varying mutated tau levels in the pre-incubation step caused different average velocity levels parallel to the mutated tau concentration.
This study demonstrates the previously proposed tau detection method in an on-chip format. Moreover, additional pre-incubation step can solve issues on detecting mutated tau while amplifying the sensitivity towards physiological levels. After necessary optimizations, clinical samples (e.g. cerebrospinal fluid) should be used to test the performance for demonstrating the diagnostic capabilities.
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