1. Oligodendrocytes produce amyloid-β and contribute to plaque formation alongside neurons in Alzheimer's disease model mice.
- Author
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Sasmita AO, Depp C, Nazarenko T, Sun T, Siems SB, Ong EC, Nkeh YB, Böhler C, Yu X, Bues B, Evangelista L, Mao S, Morgado B, Wu Z, Ruhwedel T, Subramanian S, Börensen F, Overhoff K, Spieth L, Berghoff SA, Sadleir KR, Vassar R, Eggert S, Goebbels S, Saito T, Saido T, Saher G, Möbius W, Castelo-Branco G, Klafki HW, Wirths O, Wiltfang J, Jäkel S, Yan R, and Nave KA
- Subjects
- Animals, Humans, Mice, Amyloid beta-Protein Precursor metabolism, Amyloid beta-Protein Precursor genetics, Disease Models, Animal, Mice, Transgenic, Alzheimer Disease metabolism, Alzheimer Disease pathology, Alzheimer Disease genetics, Amyloid beta-Peptides metabolism, Amyloid Precursor Protein Secretases metabolism, Aspartic Acid Endopeptidases metabolism, Neurons metabolism, Neurons pathology, Oligodendroglia metabolism, Oligodendroglia pathology, Plaque, Amyloid pathology, Plaque, Amyloid metabolism
- 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., (© 2024. The Author(s).)- Published
- 2024
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