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

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

Nature neuroscience (2024-08-06)
Andrew Octavian Sasmita, Constanze Depp, Taisiia Nazarenko, Ting Sun, Sophie B Siems, Erinne Cherisse Ong, Yakum B Nkeh, Carolin Böhler, Xuan Yu, Bastian Bues, Lisa Evangelista, Shuying Mao, Barbara Morgado, Zoe Wu, Torben Ruhwedel, Swati Subramanian, Friederike Börensen, Katharina Overhoff, Lena Spieth, Stefan A Berghoff, Katherine Rose Sadleir, Robert Vassar, Simone Eggert, Sandra Goebbels, Takashi Saito, Takaomi Saido, Gesine Saher, Wiebke Möbius, Gonçalo Castelo-Branco, Hans-Wolfgang Klafki, Oliver Wirths, Jens Wiltfang, Sarah Jäkel, Riqiang Yan, Klaus-Armin Nave
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Actin antibody, Mouse monoclonal, clone AC-40, purified from hybridoma cell culture
Sigma-Aldrich
Anti-Presenilin-1 Antibody, NT, clone hPS1-NT, culture supernatant, clone hPS1-NT, Chemicon®
Sigma-Aldrich
Anti-APP Antibody, clone 1D1, clone 1D1, from rat