Oligodendrocytes produce amyloid-β and contribute to plaque formation alongside neurons in Alzheimer’s disease model mice
Andrew Octavian Sasmita, Constanze Depp, T. I. Nazarenko, Ting Sun, Sophie B. Siems, Erinne Cherisse Ong, Yakum Bertrand Nkeh, Carolin Böhler, Xuan Yu, Bastian Bues, Lisa Evangelista, Shuying Mao, Bárbara Morgado, Zoe Y. Wu, Torben Ruhwedel, Swati Subramanian, Friederike Börensen, Katharina Overhoff, Lena Spieth, Stefan A. Berghoff, Katherine R. Sadleir, Robert Vassar, Simone Eggert, Sandra Goebbels, Takashi Saito, Takaomi C. Saido, Gesine Saher, Wiebke Möbius, Gonçalo Castelo‐Branco, Hans‐Wolfgang Klafki, Oliver Wirths, Jens Wiltfang, Sarah Jäkel, Riqiang Yan, Klaus‐Armin Nave
Abstract
Abstract Amyloid-β (Aβ) is thought to be neuronally derived in Alzheimer’s disease (AD). However, transcripts of amyloid precursor protein ( APP ) and amyloidogenic enzymes are equally abundant in oligodendrocytes (OLs). By cell-type-specific deletion of Bace1 in a humanized knock-in AD model, APP NLGF , we demonstrate that OLs and neurons contribute to Aβ plaque burden. For rapid plaque seeding, excitatory projection neurons must provide a threshold level of Aβ. Ultimately, our findings are relevant for AD prevention and therapeutic strategies.