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Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E

Author

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  • Steven W. Barger

    (Cell Biology, and Neurobiology, University of Arkansas for Medical Sciences
    Geriatric Research Education and Clinical Center, John L. McClellan Memorial Veterans Affairs Medical Center)

  • Ashley D. Harmon

    (Geriatric Research Education and Clinical Center, John L. McClellan Memorial Veterans Affairs Medical Center)

Abstract

A role for β-amyloid precursor protein (β-APP) in the development of Alzheimer's disease has been indicated by genetics1, and many conditions in which β-APP is raised have been associated with an increased risk of Alzheimer's disease or an Alzheimer's-like pathology2,3,4. Inflammatory events may also contribute to Alzheimer's disease5. Here we investigate whether a secreted derivative of β-APP (sAPP-α) can induce inflammatory reactions in microglia, which are brain cells of monocytic lineage. We found that treatment with sAPP-α increased markers of activation in microglia and enhanced their production of neurotoxins. The ability of sAPP-α to activate microglia was blocked by prior incubation of the protein with apolipoprotein E3 but not apolipoprotein E4, a variant associated with an increased risk for Alzheimer's6. A product of amyloidogenic β-APP processing (sAPP-β) also activated microglia. Because sAPP-β is deficient in the neuroprotective activity shown by sAPP-α, our results indicate that increased amyloidogenic processing could adversely affect the balance of sAPP activities that determine neuronal viability.

Suggested Citation

  • Steven W. Barger & Ashley D. Harmon, 1997. "Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E," Nature, Nature, vol. 388(6645), pages 878-881, August.
    • Handle: RePEc:nat:nature:v:388:y:1997:i:6645:d:10.1038_42257
    DOI: 10.1038/42257
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    Cited by:

    1. Jean-Noël Houchat & Alison Cartereau & Anaïs Le Mauff & Emiliane Taillebois & Steeve H. Thany, 2020. "An Overview on the Effect of Neonicotinoid Insecticides on Mammalian Cholinergic Functions through the Activation of Neuronal Nicotinic Acetylcholine Receptors," IJERPH, MDPI, vol. 17(9), pages 1-11, May.

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