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Neuroinflammation in Alzheimer's disease.
Literature Information
| PMID | 25792098 |
|---|---|
| Journal | The Lancet. Neurology |
| Impact Factor | 45.5 |
| JCR Quartile | Q1 |
| Publication Year | 2015 |
| Times Cited | 2901 |
| Keywords | Neuroinflammation, Alzheimer's disease, Immune mechanisms, Inflammatory mediators, Risk factors |
| Literature Type | Journal Article, Review |
| ISSN | 1474-4422 |
| Pages | 388-405 |
| Issue | 14(4) |
| 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 |
TL;DR
This research highlights that Alzheimer's disease involves significant interactions between neuronal and immunological processes, where misfolded proteins activate microglia and astroglia, leading to inflammation that exacerbates the disease. The findings suggest that genetic risk factors and external influences like systemic inflammation could be targeted to develop new therapeutic and preventive strategies for Alzheimer's disease.
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Neuroinflammation · Alzheimer's disease · Immune mechanisms · Inflammatory mediators · Risk factors
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.
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Primary Questions Addressed
- How do specific inflammatory mediators released during neuroinflammation influence the progression of Alzheimer's disease?
- What role do genetic factors play in the regulation of glial clearance of misfolded proteins in Alzheimer's disease?
- How might systemic inflammation and obesity interact with neuroinflammatory processes in the brain to affect Alzheimer's disease outcomes?
- What are the potential therapeutic strategies that could target the immune mechanisms involved in Alzheimer's disease?
- In what ways can understanding neuroinflammation lead to preventive measures against Alzheimer's disease in at-risk populations?
Key Findings
Research Background and Purpose
Alzheimer's disease (AD) has traditionally been viewed as a neurodegenerative disorder primarily affecting neurons. However, recent evidence indicates that the pathogenesis of AD is significantly influenced by immunological mechanisms in the brain. The purpose of this research is to explore the interactions between misfolded proteins, immune responses, and external factors like systemic inflammation and obesity, which may contribute to the progression of Alzheimer's disease.
Main Methods/Materials/Experimental Design
The study employs a genome-wide analysis to identify genes associated with sporadic Alzheimer's disease. It focuses on the role of glial cells, specifically microglia and astroglia, in the clearance of misfolded proteins and the initiation of inflammatory responses. The research also examines how external factors such as obesity and systemic inflammation can disrupt these immune processes.
Key Results and Findings
- Immune Response Activation: Misfolded and aggregated proteins activate pattern recognition receptors on microglia and astroglia, triggering an innate immune response characterized by the release of inflammatory mediators.
- Gene Identification: Genome-wide analysis identified several genes that increase the risk of sporadic Alzheimer's disease, many of which are involved in regulating glial clearance and inflammatory responses.
- Influence of External Factors: Systemic inflammation and obesity were found to negatively affect the brain's immunological processes, potentially accelerating the progression of Alzheimer's disease.
Main Conclusions/Significance/Innovation
The findings highlight the importance of glial cells and the immune response in the pathogenesis of Alzheimer's disease, suggesting that AD is not solely a neuronal disorder but involves significant immunological components. This research opens new avenues for therapeutic and preventive strategies targeting immune mechanisms and modulating risk factors, such as inflammation and obesity, to potentially alter the course of the disease.
Research Limitations and Future Directions
- Limitations: The study primarily relies on genome-wide association studies, which may not fully capture the complexity of gene-environment interactions in AD. Additionally, the specific mechanisms through which external factors influence glial function require further elucidation.
- Future Directions: Future research should focus on developing interventions that target immune responses in the brain, exploring the role of lifestyle modifications in mitigating risk factors, and conducting longitudinal studies to better understand the temporal relationships between immune activation and Alzheimer's disease progression.
References
- Inflammasome activation and IL-1β and IL-18 processing during infection. - Frank L van de Veerdonk;Mihai G Netea;Charles A Dinarello;Leo A B Joosten - Trends in immunology (2011)
- Alzheimer's disease. - Henry W Querfurth;Frank M LaFerla - The New England journal of medicine (2010)
- Heme binding induces dimerization and nitration of truncated β-amyloid peptide Aβ16 under oxidative stress. - Grégory Thiabaud;Silvia Pizzocaro;Ricardo Garcia-Serres;Jean-Marc Latour;Enrico Monzani;Luigi Casella - Angewandte Chemie (International ed. in English) (2013)
- Nonsteroidal anti-inflammatory drugs and peroxisome proliferator-activated receptor-gamma agonists modulate immunostimulated processing of amyloid precursor protein through regulation of beta-secretase. - Magdalena Sastre;Ilse Dewachter;Gary E Landreth;Timothy M Willson;Thomas Klockgether;Fred van Leuven;Michael T Heneka - The Journal of neuroscience : the official journal of the Society for Neuroscience (2003)
- Rosiglitazone monotherapy in mild-to-moderate Alzheimer's disease: results from a randomized, double-blind, placebo-controlled phase III study. - Michael Gold;Claire Alderton;Marina Zvartau-Hind;Sally Egginton;Ann M Saunders;Michael Irizarry;Suzanne Craft;Gary Landreth;Ulla Linnamägi;Sharon Sawchak - Dementia and geriatric cognitive disorders (2010)
- Physiology of microglia. - Helmut Kettenmann;Uwe-Karsten Hanisch;Mami Noda;Alexei Verkhratsky - Physiological reviews (2011)
- Immunohistochemical study of the beta-chemokine receptors CCR3 and CCR5 and their ligands in normal and Alzheimer's disease brains. - M Q Xia;S X Qin;L J Wu;C R Mackay;B T Hyman - The American journal of pathology (1998)
- Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders. - Rainer Rupprecht;Vassilios Papadopoulos;Gerhard Rammes;Thomas C Baghai;Jinjiang Fan;Nagaraju Akula;Ghislaine Groyer;David Adams;Michael Schumacher - Nature reviews. Drug discovery (2010)
- Concomitant astroglial atrophy and astrogliosis in a triple transgenic animal model of Alzheimer's disease. - Markel Olabarria;Harun N Noristani;Alexei Verkhratsky;José J Rodríguez - Glia (2010)
- Body fluid cytokine levels in mild cognitive impairment and Alzheimer's disease: a comparative overview. - Frederic Brosseron;Marius Krauthausen;Markus Kummer;Michael T Heneka - Molecular neurobiology (2014)
Literatures Citing This Work
- From Molecular Circuit Dysfunction to Disease: Case Studies in Epilepsy, Traumatic Brain Injury, and Alzheimer's Disease. - Chris G Dulla;Douglas A Coulter;Jokubas Ziburkus - The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry (2016)
- The choreography of neuroinflammation in Huntington's disease. - Andrea Crotti;Christopher K Glass - Trends in immunology (2015)
- Increased Risk of Dementia in Patients With Erectile Dysfunction: A Population-Based, Propensity Score-Matched, Longitudinal Follow-Up Study. - Chun-Ming Yang;Yuan-Chi Shen;Shih-Feng Weng;Jhi-Joung Wang;Kai-Jen Tien - Medicine (2015)
- The neuropathology and cerebrovascular mechanisms of dementia. - Limor Raz;Janice Knoefel;Kiran Bhaskar - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (2016)
- Autosomal Dominant Alzheimer Disease: A Unique Resource to Study CSF Biomarker Changes in Preclinical AD. - Suzanne Elizabeth Schindler;Anne M Fagan - Frontiers in neurology (2015)
- Chronic Brain Inflammation: The Neurochemical Basis for Drugs to Reduce Inflammation. - Bevyn Jarrott;Spencer J Williams - Neurochemical research (2016)
- Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders. - Hisham Qosa;David S Miller;Piera Pasinelli;Davide Trotti - Brain research (2015)
- Brain "fog," inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin. - Theoharis C Theoharides;Julia M Stewart;Erifili Hatziagelaki;Gerasimos Kolaitis - Frontiers in neuroscience (2015)
- Molecular Targets of Cannabidiol in Neurological Disorders. - Clementino Ibeas Bih;Tong Chen;Alistair V W Nunn;Michaël Bazelot;Mark Dallas;Benjamin J Whalley - Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics (2015)
- Magnesium Lithospermate B Protects Neurons Against Amyloid β (1-42)-Induced Neurotoxicity Through the NF-κB Pathway. - Feng Jiang;Yongqiang Mao;Huixiang Liu;Ping Xu;Li Zhang;Xiaobo Qian;Xiaofeng Sun - Neurochemical research (2015)
... (2891 more literatures)
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