Osama Al-Dalahmah, Matti Lam, Julie J McInvale, Wenhui Qu, Trang Nguyen, Jeong-Yeon Mun, Sam Kwon, Nkechime Ifediora, Aayushi Mahajan, Nelson Humala, Tristan Winters, Ellen Angeles, Kelly A Jakubiak, Rebekka Kühn, Yoon A Kim, Maria Caterina De Rosa, Claudia A Doege, Fahad Paryani, Xena Flowers, Athanassios Dovas, Angeliki Mela, Hong Lu, Michael A DeTure, Jean Paul Vonsattel, Zbigniew K Wszolek, Dennis W Dickson, Tanja Kuhlmann, Holm Zaehres, Hans R Schöler, Andrew A Sproul, Markus D Siegelin, Philip L De Jager, James E Goldman, Vilas Menon, Peter Canoll, Gunnar Hargus
Frontotemporal dementia (FTD) is an incurable group of early-onset dementias that can be caused by the deposition of hyperphosphorylated tau in patient brains. However, the mechanisms leading to neurodegeneration remain largely unknown. Here, we combined single-cell analyses of FTD patient brains with a stem cell culture and transplantation model of FTD. We identified disease phenotypes in FTD neurons carrying the MAPT-N279K mutation, which were related to oxidative stress, oxidative phosphorylation, and neuroinflammation with an upregulation of the inflammation-associated protein osteopontin (OPN)...
April 10, 2024: Cell Stem Cell