Oligodendrocytes produce amyloid-β and contribute to plaque formation alongside neurons in Alzheimer’s disease model mice

Sasmita, Andrew Octavian ; Depp, Constanze ; Nazarenko, Taisiia; Sun, Ting ; Siems, Sophie B.; Ong, Erinne Cherisse ; Nkeh, Yakum B. ; Böhler, Carolin; Yu, Xuan; Bues, Bastian ; Evangelista, Lisa ; Mao, Shuying; Morgado, Barbara ; Wu, Zoe; Ruhwedel, Torben ; Subramanian, Swati; Börensen, Friederike; Overhoff, Katharina; Spieth, Lena; Berghoff, Stefan A.; Sadleir, Katherine Rose; Vassar, Robert; Eggert, Simone; Goebbels, Sandra; Saito, Takashi ; Saido, Takaomi ; Saher, Gesine ; Möbius, Wiebke ; Castelo-Branco, Gonçalo ; Klafki, Hans-Wolfgang; Wirths, Oliver ; Wiltfang, Jens ; Jäkel, Sarah; Yan, Riqiang und Nave, Klaus-Armin (2024): Oligodendrocytes produce amyloid-β and contribute to plaque formation alongside neurons in Alzheimer’s disease model mice. In: Nature Neuroscience, Bd. 27, Nr. 9: S. 1668-1674

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, APPNLGF, 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy) ; Medizin > Institut für Schlaganfall- und Demenzforschung (ISD)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1097-6256
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198