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

Publisher: Nature Publishing Group Country of Publication: United States NLM ID: 9809671 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1726 (Electronic) Linking ISSN: 10976256 NLM ISO Abbreviation: Nat Neurosci Subsets: MEDLINE

Publication: <2002->: New York, NY : Nature Publishing Group
Original Publication: New York, NY : Nature America Inc., c1998-

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; Animals ; Humans ; Mice ; Amyloid beta-Protein Precursor/metabolism ; Amyloid beta-Protein Precursor/genetics ; Disease Models, Animal ; Mice, Transgenic

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).)

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0 (Amyloid beta-Peptides)
0 (Amyloid beta-Protein Precursor)
EC 3.4.- (Amyloid Precursor Protein Secretases)
EC 3.4.23.- (Aspartic Acid Endopeptidases)
EC 3.4.23.46 (Bace1 protein, mouse)

Date Created: 20240805 Date Completed: 20240904 Latest Revision: 20240912

20240912

PMC11374705

10.1038/s41593-024-01730-3

39103558