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Comment
. 2024 Sep 12;22(9):e3002798.
doi: 10.1371/journal.pbio.3002798. eCollection 2024 Sep.

Remember oligodendrocytes: Uncovering their overlooked role in Alzheimer's disease

Lena Spieth  1   2 , Mikael Simons  1   2   3   4
Affiliations
Comment

Remember oligodendrocytes: Uncovering their overlooked role in Alzheimer's disease

Lena Spieth et al. PLoS Biol. .

Abstract

Our understanding of Alzheimer's disease (AD) has evolved from focusing solely on neurons to recognizing the role of glia. A recent study in PLOS Biology revealed that oligodendrocytes are an important source of Aβ that impairs neuronal function.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Amyloidogenic processing of the amyloid precursor protein (APP) in oligodendrocytes and its effects on neuronal activity.
The transmembrane protein APP is sequentially cleaved by β-secretase (BACE1) and γ-secretase (PSEN1/2) in oligodendrocytes leading to the particular high Aβ42/40 ratios. The Aβ peptides released have the ability to aggregate into oligomers, which can lead to synaptic dysfunction accompanied by neuronal hyperactivity (graphics created with biorender.com).
See this image and copyright information in PMC

Comment on

References

    1. De Strooper B, Karran E. The Cellular Phase of Alzheimer’s Disease. Cell. 2016;164(4):603–615. Epub 2016/02/13. doi: 10.1016/j.cell.2015.12.056 . - DOI - PubMed
    1. Rajani RM, Ellingford R, Hellmuth M, Harris SS, Taso OS, Graykowski D et al. Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s Disease. PLoS Biol. 2024; 22(7):e3002727. doi: 10.1371/journal.pbio.3002727 - DOI - PMC - PubMed
    1. Sasmita AO, Depp C, Nazarenko T, Sun T, Siems SB, Ong EC, Nkeh YB et al. Oligodendrocytes and neurons contribute to amyloid-β deposition in Alzheimer’s disease. Nat Neurosci. 2024. doi: 10.1038/s41593-024-01730-3 - DOI - PMC - PubMed
    1. Zhang Y, Chen K, Sloan SA, Bennett ML, Scholze AR, O’Keeffe S, et al. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci. 2014;34(36):11929–11947. doi: 10.1523/JNEUROSCI.1860-14.2014 ; PubMed Central PMCID: PMC4152602. - DOI - PMC - PubMed
    1. Sharma K, Schmitt S, Bergner CG, Tyanova S, Kannaiyan N, Manrique-Hoyos N, et al. Cell type- and brain region-resolved mouse brain proteome. Nat Neurosci. 2015;18(12):1819–1831. doi: 10.1038/nn.4160 . - DOI - PMC - PubMed

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