Rocio Vicario, Stamatina Fragkogianni, Leslie Weber, Tomi Lazarov, Yang Hu, Samantha Y Hayashi, Barbara P Craddock, Nicholas D Socci, Araitz Alberdi, Ann Baako, Oyku Ay, Masato Ogishi, Estibaliz Lopez-Rodrigo, Rajya Kappagantula, Agnes Viale, Christine A Iacobuzio-Donahue, Ting Zhou, Richard M Ransohoff, Richard Chesworth, Omar Abdel-Wahab, Bertrand Boisson, Olivier Elemento, Jean-Laurent Casanova, W Todd Miller, Frederic Geissmann
Somatic genetic heterogeneity resulting from post-zygotic DNA mutations is widespread in human tissues and can cause diseases, however few studies have investigated its role in neurodegenerative processes such as Alzheimer's Disease (AD). Here we report the selective enrichment of microglia clones carrying pathogenic variants, that are not present in neuronal, glia/stromal cells, or blood, from patients with AD in comparison to age-matched controls. Notably, microglia-specific AD-associated variants preferentially target the MAPK pathway, including recurrent CBL ring-domain mutations...
January 25, 2024: bioRxiv