A13 | Contribution of microglia cell death to tau pathology in Alzheimer’s disease and other tauopathies
Dr. Christina Ising
CECAD, University of Cologne
SFB1403 Junior Group
Contact: cising2(at)uni-koeln(dot)de
For more information visit: Ising Lab
Abstract
This project is funded within the 2nd funding period of the SFB 1403, starting from 2024
Alzheimer’s disease, a tauopathy and the most common form of dementia, is characterized by accumulation of extracellular amyloid-beta and intracellular tau as well as a chronic neuroinflammation. Microglia, the innate immune cells of the brain, can be activated by tau and potentially undergo pyroptotic cell death, mediated via the NLRP3 inflammasome. However, the underlying mechanisms and the contribution of microglial pyroptosis to the disease remain elusive. By combining mouse models with primary cell culture, this project will investigate how pyroptotic cell death and especially the pyroptotic pore protein Gasdermin D (GSDMD) are involved in the development and progression Alzheimer’s disease and other tauopathies.
Recent Publications
Project A14 Publications 2nd Funding Period 2024 - 2027
2024
Karabag D, Heneka MT, Ising C. The putative contribution of cellular senescence to driving tauopathies. Trends Immunol. 2024 Oct;45(10):837-848. doi: 10.1016/j.it.2024.08.006. Epub 2024 Sep 20. PMID: 39306559.
Project related Publications
2018 - 2021
Shi, Y., Andhey, P.S., Ising, C., Wang, K., Snipes, L.L., Boyer, K., Lawson, S., Yamada, K., Qin, W., Manis, M., Serrano, J.R., Benitez, B.A., Schmidt, R.E., Artyomov, M., Ulrich, J.D., and Holtzman, D.M. (2021). Overexpressing low-density lipoprotein receptor reduces tau-associated neurodegeneration in relation to apoE-linked mechanisms. Neuron 109, 2413-2426.e7.
Ising, C., Venegas, C., Zhang, S., Scheiblich, H., Schmidt, S.V., Vieira-Saecker, A., Schwartz, S., Albasset, S., McManus, R.M., Tejera, D., …, Latz, E., Buée, L., and Heneka, M.T. (2019). NLRP3 inflammasome activation drives tau pathology. Nature 575, 669–673.
Ising, C., and Heneka, M.T. (2018). Functional and structural damage of neurons by innate immune mechanisms during neurodegeneration. Cell Death Dis. 9, 120.