Neuroinflammation in Alzheimer's disease

Michael T. Heneka, Monica J. Carson, Joseph El Khoury, Gary E. Landreth, Frederic Brosseron, Douglas L. Feinstein, Andreas H. Jacobs, Tony Wyss-Coray, Javier Vitorica, Richard M. Ransohoff, Karl Herrup, Sally A. Frautschy, Bente Finsen, Guy C. Brown, Alexei Verkhratsky, Koji Yamanaka, Jari Koistinaho, Eicke Latz, Annett Halle, Gabor C. PetzoldTerrence Town, Dave Morgan, Mari L. Shinohara, V. Hugh Perry, Clive Holmes, Nicolas G. Bazan, David J. Brooks, Stéphane Hunot, Bertrand Joseph, Nikolaus Deigendesch, Olga Garaschuk, Erik Boddeke, Charles A. Dinarello, John C. Breitner, Greg M. Cole, Douglas T. Golenbock, Markus P. Kummer

Research output: Contribution to journalReview article

Abstract

Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)388-405
Number of pages18
JournalThe Lancet Neurology
Volume14
Issue number4
DOIs
StatePublished - Apr 1 2015

ASJC Scopus subject areas

  • Clinical Neurology

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  • Cite this

    Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., Herrup, K., Frautschy, S. A., Finsen, B., Brown, G. C., Verkhratsky, A., Yamanaka, K., Koistinaho, J., Latz, E., Halle, A., ... Kummer, M. P. (2015). Neuroinflammation in Alzheimer's disease. The Lancet Neurology, 14(4), 388-405. https://doi.org/10.1016/S1474-4422(15)70016-5