Yuxi Liu, Witty Kwok, Hyojung Yoon, Jae Cheon Ryu, Patrick Stevens, Tara R Hawkinson, Cameron J Shedlock, Roberto A Ribas, Terrymar Medina, Shannon B Keohane, Douglas Scharre, Lei Bruschweiler-Li, Rafael Bruschweiler, Alban Gaultier, Karl Obrietan, Ramon C Sun, Sung Ok Yoon
Microglia undergo two-stage activation in neurodegenerative diseases, known as disease-associated microglia (DAM). TREM2 mediates the DAM2 stage transition, but what regulates the first DAM1 stage transition is unknown. We report that glucose dyshomeostasis inhibits DAM1 activation, and PKM2 plays a role. As in tumors, PKM2 was aberrantly elevated in both male and female human AD brains, but unlike in tumors, it is expressed as active tetramers, as well as among TREM2+ microglia surrounding plaques in 5XFAD male and female mice...
April 2, 2024: Journal of Neuroscience