Alzheimer’s (AD) is a type of dementia that affects memory, thinking and behavior. AD has no cure and is at the forefront of biomedical research today. AD is cause by hippocampal and cortical neurons degeneration. Their degeneration result in part from hyperphosphorylation of Tau, key peptide  involved in AD. Currently, scientists still do not know what causes the hyperphosphorylation of Tau and its mechanism on hippocampal and cortical neurons. 

We have developed at NETRI microfluidic devices with a triangular architecture to quantify the degeneration of neurons depending on an abnormal hyperphoporylated form of Tau.

CAPABILITIES Growth kinetics, Co-culture, hiPSC Derived Cell, Readouts
CHIP DuaLink Delta Ultra
CELL TYPE Glutamatergic Neurons
RESOURCES Publications, Application Note, Application Protocol, Posters, Cells DataSheet
(FujiFilm CDI, BrainXell), Chip DataSheet
Takeda, S., Wegmann, S., Cho, H., Devos, S. L., Commins, C., Roe, A. D., Nicholls, S. B., Carlson, G. A., Pitstick, R., Nobuhara, C. K., Costantino, I., Frosch, M. P., Muller, D. J., Irimia, D., & Hyman, B. T. (2015). Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer’s disease brain. Nature Communications, 6.

Kunze, A., Meissner, R., Brando, S., & Renaud, P. (2011). Co-pathological connected primary neurons in a microfluidic device for Alzheimer studies. Biotechnology and Bioengineering, 108(9), 2241–2245.

Stoothoff, W., Jones, P. B., Spires-Jones, T. L., Joyner, D., Chhabra, E., Bercury, K., Fan, Z., Xie, H., Bacskai, B., Edd, J., Irimia, D., & Hyman, B. T. (2009). Differential effect of three-repeat and four-repeat tau on mitochondrial axonal transport. Journal of Neurochemistry, 111(2), 417–427.

Katsikoudi, A., Ficulle, E., Cavallini, A., Sharman, G., Guyot, A., Zagnoni, M., Eastwood, B. J., Hutton, M., & Bose, S. (2020). Quantitative propagation of assembled human Tau from Alzheimer’s disease brain in microfluidic neuronal cultures. Journal of Biological Chemistry, jbc.RA120.013325.

Wu, J. W., Herman, M., Liu, L., Simoes, S., Acker, C. M., Figueroa, H., Steinberg, J. I., Margittai, M., Kayed, R., Zurzolo, C., Di Paolo, G., & Duff, K. E. (2013). Small misfolded tau species are internalized via bulk endocytosis and anterogradely and retrogradely transported in neurons. Journal of Biological Chemistry, 288(3), 1856–1870.

Usenovic, M., Niroomand, S., Drolet, R. E., Yao, L., Gaspar, R. C., Hatcher, N. G., Schachter, J., Renger, J. J., & Parmentier-Batteur, S. (2015). Internalized tau oligomers cause neurodegeneration by inducing accumulation of pathogenic tau in human neurons derived from induced pluripotent stem cells. Journal of Neuroscience, 35(42), 14234–14250.

Wu, J. W., Hussaini, S. A., Bastille, I. M., Rodriguez, G. A., Mrejeru, A., Rilett, K., Sanders, D. W., Cook, C., Fu, H., Boonen, R. A. C. M., Herman, M., Nahmani, E., Emrani, S., Figueroa, Y. H., Diamond, M. I., Clelland, C. L., Wray, S., & Duff, K. E. (2016). Neuronal activity enhances tau propagation and tau pathology in vivo. Nature Neuroscience, 19(8), 1085–1092.

Wang, Y., Balaji, V., Kaniyappan, S., Krüger, L., Irsen, S., Tepper, K., Chandupatla, R., Maetzler, W., Schneider, A., Mandelkow, E. E. M. E. E. M. E., & Mandelkow, E. E. M. E. E. M. E. (2017). The release and trans-synaptic transmission of Tau via exosomes. Molecular Neurodegeneration, 12(1), 1–25.

Nobuhara, C. K., DeVos, S. L., Commins, C., Wegmann, S., Moore, B. D., Roe, A. D., Costantino, I., Frosch, M. P., Pitstick, R., Carlson, G. A., Hock, C., Nitsch, R. M., Montrasio, F., Grimm, J., Cheung, A. E., Dunah, A. W., Wittmann, M., Bussiere, T., Weinreb, P. H., … Takeda, S. (2017). Tau Antibody Targeting Pathological Species Blocks Neuronal Uptake and Interneuron Propagation of Tau in Vitro. American Journal of Pathology, 187(6), 1399–1412.
READINESS LEVEL ④/ ⑧ Protocol done

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