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

2024/08/05 by Andrew Octavian Sasmita, Constanze Depp, T. I. Nazarenko +32 · 1 voice · 2 citations
Medicine · Neuroscience · #Alzheimer's disease research and treatments #Neurogenesis and neuroplasticity mechanisms #Neuroinflammation and Neurodegeneration Mechanisms

paper · pdf · doi:10.1038/s41593-024-01730-3

openalex publication_date 2024/08/05 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31

Abstract

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.

Citations

• Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease
• Integrated analysis of multimodal single-cell data

Cited by

• Disruption of hnRNP A2-mediated RNA dynamics by amyloid-β drives MBP increase in Alzheimer’s disease
• Amyloid‐β Seeds in Alzheimer's Disease: Research Challenges and Implications

Discussions

• On World Alzheimer’s Day, we recognize the cutting-edge research presented in this Nature Neuro publication. #RNAscope Multiplex Fluorescent assay was used to identify APP and BACE1 expressing oligode [bsky, 1 points, 0 comments]

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