Neuroinflammation in Alzheimer's disease.

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.

• Authors: 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 Petzold, Terrence 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
• Journal: The Lancet. Neurology (Lancet Neurol) Vol. 14 Issue 4 Pg. 388-405 (Apr 2015) ISSN: 1474-4465 [Electronic] England
• PMID: 25792098 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Biomarkers
• Inflammation Mediators
• Nootropic Agents

Topics

• Alzheimer Disease (genetics, immunology, metabolism, pathology, prevention & control)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Astrocytes (immunology, pathology)
• Biomarkers (blood, cerebrospinal fluid)
• Brain Injuries (complications, metabolism)
• Clinical Trials as Topic
• Disease Models, Animal
• Disease Progression
• Humans
• Immunity, Innate
• Immunization
• Inflammation (diagnosis, immunology, metabolism)
• Inflammation Mediators (immunology, metabolism)
• Locus Coeruleus (pathology)
• Microglia (immunology, pathology)
• Nootropic Agents (administration & dosage)
• Obesity (complications, metabolism)
• Phagocytosis
• Protein Folding
• Risk Factors
• Severity of Illness Index