Journal Article

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

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

2024

Overview

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. In Alzheimer’s disease, neurons are considered the sole source of amyloid-β (Aβ) peptides that form plaques. Here the authors show that oligodendrocytes, the myelinating glial cells of the brain, also contribute to Aβ plaque burden alongside neurons.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 14 / 14/1 / 14/34 / 14/63 / 38 / 38/91 / 631/378/1689/1283 / 631/378/2596/1705 / 82 / 82/29 / 82/51 / 82/80 / Alzheimer Disease - genetics / Alzheimer Disease - metabolism / Alzheimer Disease - pathology / Alzheimer's disease / Amyloid beta-Peptides - metabolism / Amyloid beta-Protein Precursor - genetics / Amyloid beta-Protein Precursor - metabolism / Amyloid precursor protein / Amyloid Precursor Protein Secretases - metabolism / Amyloidogenesis / Animal Genetics and Genomics / Animal models / Animals / Antibodies / Aspartic Acid Endopeptidases - metabolism / Behavioral Sciences / Biochemistry / Biological Techniques / Biomedical and Life Sciences / Biomedicine / Brain research / Brief Communication / Clonal deletion / Disease / Disease Models, Animal / Glial cells / Humans / Mice / Mice, Transgenic / Neurobiology / Neurodegenerative diseases / Neurology / Neuronal-glial interactions / Neurons / Neurons - metabolism / Neurons - pathology / Neurosciences / Oligodendrocytes / Oligodendroglia - metabolism / Oligodendroglia - pathology / Peptides / Plaque, Amyloid - metabolism / Plaque, Amyloid - pathology / Protein seeding / Proteins / β-Amyloid / β-Site APP-cleaving enzyme 1