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Siglec receptors and hiding plaques in Alzheimer's disease

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Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease. One hallmark of this disease is the continuous increase in the numbers and size of aggregating amyloid plaques. The accumulation of extracellular plaques is an immunologically interesting phenomenon since microglial cells, brain-specific macrophages, should be able to cleanse the aggregating material from the human brain. Immunotherapy targeting β-amyloid peptides in plaques with antibodies represents a promising therapy in AD. Recent progress in pattern recognition receptors of monocytes and macrophages has revealed that the sialic acid-binding, immunoglobulin-like lectin (Siglec) family of receptors is an important recognition receptor for sialylated glycoproteins and glycolipids. Interestingly, recent studies have revealed that microglial cells contain only one type of Siglec receptors, Siglec-11, which mediates immunosuppressive signals and thus inhibits the function of other microglial pattern recognition receptors, such as TLRs, NLRs, and RAGE receptors. We will review here the recent literature which clearly indicates that aggregating amyloid plaques are masked in AD by sialylated glycoproteins and gangliosides. Sialylation and glycosylation of plaques, mimicking the cell surface glycocalyx, can activate the immunosuppressive Siglec-11 receptors, as well as hiding the neuritic plaques, allowing them to evade the immune surveillance of microglial cells. This kind of immune evasion can prevent the microglial cleansing process of aggregating amyloid plaques in AD.

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Acknowledgements

This study was financially supported by grants from the Academy of Finland, The Finnish Eye Foundation, and the University of Kuopio, Finland. The authors thank Dr. Ewen MacDonald for checking the language of the manuscript.

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Authors and Affiliations

  1. Department of Neurology, Institute of Clinical Medicine, University of Kuopio, P.O. Box 1627, 70211, Kuopio, Finland

    Antero Salminen

  2. Department of Neurology, University Hospital of Kuopio, P.O. Box 1777, 70211, Kuopio, Finland

    Antero Salminen

  3. Department of Ophthalmology, Institute of Clinical Medicine, University of Kuopio, P.O. Box 1627, 70211, Kuopio, Finland

    Kai Kaarniranta

  4. Department of Ophthalmology, University Hospital of Kuopio, P.O. Box 1777, 70211, Kuopio, Finland

    Kai Kaarniranta

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  1. Antero Salminen
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Correspondence to Antero Salminen.

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Salminen, A., Kaarniranta, K. Siglec receptors and hiding plaques in Alzheimer's disease. J Mol Med 87, 697–701 (2009). https://doi.org/10.1007/s00109-009-0472-1

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  • DOI: https://doi.org/10.1007/s00109-009-0472-1

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