Infection, systemic inflammation, and Alzheimer's disease

Lim, Siok Lam; Rodriguez‐Ortiz, Carlos J.; Kitazawa, Masashi

doi:10.1016/j.micinf.2015.04.004

Cited by 87 publications

(71 citation statements)

References 81 publications

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“…The OR of prior RA for patients with AD was 0.73 (95% CI: 0.55~0.98) compared to those patients without AD after adjusting for patients’ geographic location, urbanization level, and comorbidities. To the best of our knowledge, only a few studies [7,8,17,18] have attempted to investigate the potential association between prior RA and AD, even though these two diseases supposedly share similar pathological pathways.…”

Section: Discussionmentioning

confidence: 99%

“…Although the genuine mechanisms of AD are still under discussion, many studies have reported that a cytokine-mediated inflammatory pathway is associated with the progression of cognitive impairment and AD [17,18]. Therefore, some of the prior literature investigated the potential association between RA and AD because these two diseases may share similar inflammatory mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Rheumatoid Arthritis Was Negatively Associated with Alzheimer’s Disease: A Population-Based Case-Control Study

et al. 2016

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Some of the prior literature investigated the potential association between rheumatoid arthritis (RA) and Alzheimer's disease (AD) because these two diseases may share similar inflammatory mechanisms. Nevertheless, to date, findings of the previous literature are still controversial, and some methodological limitations were observed in those studies. The aim of this case-control study was to investigate the relationship between prior RA and AD using a large population-based dataset. This study used the Taiwan Longitudinal Health Insurance Database 2005. We included 2271 patients with AD who had received prescriptions for acetylcholinesterase inhibitors (AChEIs) as cases and 6813 patients without AD as controls in this study. In addition, we performed a conditional logistic regression to examine the odds ratio (OR) and 95% confidence interval (CI) for prior RA between cases and controls. The study found that 330 (3.63%) of the total sampled patients had an RA diagnosis before the index date. Additionally, prior RA was found in 60 (2.64%) cases and in 270 (3.96%) controls. The conditional logistic regression analysis showed that the crude OR of prior RA for cases was 0.66 (95% confidence interval (CI): 0.49~0.87) compared to controls. After adjusting for patients’ geographic location, urbanization level, and comorbidities, the adjusted OR of prior RA for patients with AD was 0.73 (95% CI: 0.55~0.98) compared to those without AD. We concluded that there was an inverse association between prior RA and AD even after adjusting for potential confounders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rheumatoid Arthritis Was Negatively Associated with Alzheimer’s Disease: A Population-Based Case-Control Study

et al. 2016

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“…What is generally not appreciated is that a major secretory product of the GI tract microbiome is amyloid, and that the life-long contribution of microbial amyloid to CNS pathophysiology can be very substantial. “Amyloid” is a generic term for any aggregated, insoluble, lipoprotein-enriched deposit that exhibits β-pleated sheet structures oriented perpendicular to the fibrillar axis (Lukiw, 2012; Clark and Vissel, 2015; Lim et al, 2015; Andreeva et al, 2017; Bolós et al, 2017). The potential for amyloid formation is surprisingly high in almost all proteins; a major factor for amyloid formation is the presence within proteins of primary amino acid sequences that can form a tight, self-complementary interface with an identical segment, thus permitting the cooperative formation of a steric zipper.…”

Section: Amyloidsmentioning

confidence: 99%

Secretory Products of the Human GI Tract Microbiome and Their Potential Impact on Alzheimer's Disease (AD): Detection of Lipopolysaccharide (LPS) in AD Hippocampus

Zhao

Jaber

Lukiw

2017

Front. Cell. Infect. Microbiol.

285

307

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Although the potential contribution of the human gastrointestinal (GI) tract microbiome to human health, aging, and disease is becoming increasingly acknowledged, the molecular mechanics and signaling pathways of just how this is accomplished is not well-understood. Major bacterial species of the GI tract, such as the abundant Gram-negative bacilli Bacteroides fragilis (B. fragilis) and Escherichia coli (E. coli), secrete a remarkably complex array of pro-inflammatory neurotoxins which, when released from the confines of the healthy GI tract, are pathogenic and highly detrimental to the homeostatic function of neurons in the central nervous system (CNS). For the first time here we report the presence of bacterial lipopolysaccharide (LPS) in brain lysates from the hippocampus and superior temporal lobe neocortex of Alzheimer's disease (AD) brains. Mean LPS levels varied from two-fold increases in the neocortex to three-fold increases in the hippocampus, AD over age-matched controls, however some samples from advanced AD hippocampal cases exhibited up to a 26-fold increase in LPS over age-matched controls. This “Perspectives” paper will further highlight some very recent research on GI tract microbiome signaling to the human CNS, and will update current findings that implicate GI tract microbiome-derived LPS as an important internal contributor to inflammatory degeneration in the CNS.

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“…Recently, a group of pathogenic agents including Borrelia burgdorferi, Porphyromonas gingivalis, Chlamydophila pneumoniae, Helicobacter pylori , Cytomegalovirus, Herpes simplex virus type 1, Epstein-Bar virus, Human herpes virus 6, Candida glabrata , and Toxoplasma gondii have been addressed to have a significant effect on the late onset of AD in adults (LOAD; Bu et al, 2015; Lim et al, 2015; Figure 2). The late-age development of AD is purposely due to the activity of infections that initially occurred during the childhood (Khachaturian, 1985).…”

Section: The Impact Of Infectious Diseases On the Incidence Of Neurodmentioning

confidence: 99%

“…Viral infections either directly or indirectly contribute to AD pathogenesis through various pathways such as increasing the concentration of amyloids, phosphorylating certain neuronal proteins and afflicting neurons with injury. For instance, infections with cytomegaloviruses generate a systematic population of pro-inflammatory cytokines which can pass BBB, trigger the CNS neurodegeneration and lead to AD (Lim et al, 2015). HSV-1 is usually found in the brain of infected adult hosts (Wozniak et al, 2005) and is thought to be involved in development of AD in this group of patients (Agostini et al, 2014).…”

Section: The Relationship Between Viral Infections and Neuroinflammatmentioning

confidence: 99%

Neuroinflammation and Infection: Molecular Mechanisms Associated with Dysfunction of Neurovascular Unit

Tohidpour

Моргун

Boitsova

et al. 2017

Front. Cell. Infect. Microbiol.

124

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Neuroinflammation is a complex inflammatory process in the central nervous system, which is sought to play an important defensive role against various pathogens, toxins or factors that induce neurodegeneration. The onset of neurodegenerative diseases and various microbial infections are counted as stimuli that can challenge the host immune system and trigger the development of neuroinflammation. The homeostatic nature of neuroinflammation is essential to maintain the neuroplasticity. Neuroinflammation is regulated by the activity of neuronal, glial, and endothelial cells within the neurovascular unit, which serves as a “platform” for the coordinated action of pro- and anti-inflammatory mechanisms. Production of inflammatory mediators (cytokines, chemokines, reactive oxygen species) by brain resident cells or cells migrating from the peripheral blood, results in the impairment of blood-brain barrier integrity, thereby further affecting the course of local inflammation. In this review, we analyzed the most recent data on the central nervous system inflammation and focused on major mechanisms of neurovascular unit dysfunction caused by neuroinflammation and infections.

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Infection, systemic inflammation, and Alzheimer's disease

Cited by 87 publications

References 81 publications

Rheumatoid Arthritis Was Negatively Associated with Alzheimer’s Disease: A Population-Based Case-Control Study

Rheumatoid Arthritis Was Negatively Associated with Alzheimer’s Disease: A Population-Based Case-Control Study

Secretory Products of the Human GI Tract Microbiome and Their Potential Impact on Alzheimer's Disease (AD): Detection of Lipopolysaccharide (LPS) in AD Hippocampus

Neuroinflammation and Infection: Molecular Mechanisms Associated with Dysfunction of Neurovascular Unit

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