Apolipoprotein E (APOE) is the most abundant apolipoprotein in the brain, where it is primarily expressed and secreted by astrocytes and microglia. APOE seems to exert immunomodulatory effects in an isoform-dependent way, and a new study indicates that the APOE isoform dictates the glycosylation state and secretion of this apolipoprotein.
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References
Yamazaki, Y., Zhao, N., Caulfield, T. R., Liu, C. C. & Bu, G. Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies. Nat. Rev. Neurol. 15, 501–518 (2019).
Kloske, C. M. & Wilcock, D. M. The important interface between apolipoprotein E and neuroinflammation in Alzheimer’s disease. Front. Immunol. 11, 754 (2020).
Lanfranco, M. F., Sepulveda, J., Kopetsky, G. & Rebeck, G. W. Expression and secretion of apoE isoforms in astrocytes and microglia during inflammation. Glia https://doi.org/10.1002/glia.23974 (2021).
Zhang, Y. et al. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J. Neurosci. 34, 11929–11947 (2014).
Lynch, J. R. et al. APOE genotype and an ApoE-mimetic peptide modify the systemic and central nervous system inflammatory response. J. Biol. Chem. 278, 48529–48533 (2003).
Shi, Y. et al. ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy. Nature 549, 523–527 (2017).
Julia, T. C. W. et al. Cholesterol and matrisome pathways dysregulated in human APOE ε4 glia. Preprint at bioRxiv https://doi.org/10.1101/713362 (2019).
Yin, C. et al. ApoE attenuates unresolvable inflammation by complex formation with activated C1q. Nat. Med. 25, 496–506 (2019).
Hong, S. et al. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science 352, 712–716 (2016).
Trumble, B. C. et al. Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden. FASEB J. 31, 1508–1515 (2017).
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Hasel, P., Liddelow, S.A. Isoform-dependent APOE secretion modulates neuroinflammation. Nat Rev Neurol 17, 265–266 (2021). https://doi.org/10.1038/s41582-021-00483-y
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DOI: https://doi.org/10.1038/s41582-021-00483-y
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