Systemic infection, interleukin 1beta, and cognitive decline in Alzheimer's disease

Holmes, Clive; El-Okl, Mohammed; Williams, Amy L.; Cunningham, Colm; Wilcockson, David; Perry, V. Hugh

doi:10.1136/jnnp.74.6.788

Cited by 303 publications

(228 citation statements)

References 8 publications

Supporting

Mentioning

219

Contrasting

Unclassified

Order By: Relevance

“…Episodes of delirium significantly increase the risk of dementia (Rockwood et al, 1999), shorten the time to permanent institutionalization (Pitkala et al, 2005), and are associated with long-term functional decline (Murray et al, 1993) and increased mortality (Rockwood et al, 1999). There is also epidemiological and clinical evidence that infections accelerate the progression of AD (Holmes et al, 2003;Dunn et al, 2005). Together, these studies indicate that insults that trigger delirium, such as infection, accelerate the neurodegenerative process.…”

Section: Mechanisms and Implicationsmentioning

confidence: 85%

Central and Systemic Endotoxin Challenges Exacerbate the Local Inflammatory Response and Increase Neuronal Death during Chronic Neurodegeneration

Cunningham¹,

Wilcockson²,

Campion³

et al. 2005

J. Neurosci.

673

575

View full text Add to dashboard Cite

The contribution of inflammation to the progression of neurodegenerative diseases such as Alzheimer's, Parkinson's, and prion diseases is poorly understood. Brain inflammation in animal models of these diseases is dominated by chronic microglial activation with minimal proinflammatory cytokine expression. However, these inflammatory cells are "primed" to produce exaggerated inflammatory responses to subsequent lipopolysaccharide (LPS) challenges. We show that, using the ME7 model of prion disease, intracerebral challenge with LPS results in dramatic interleukin-1␤ (IL-1␤) expression, neutrophil infiltration, and inducible nitric oxide synthase expression in the brain parenchyma of prion-diseased mice compared with the same challenge in normal mice. Systemic inflammation evoked by LPS also produced greater increases in proinflammatory cytokines, pentraxin 3, and inducible nitric oxide synthase transcription in priondiseased mice than in control mice and induced microglial expression of IL-1␤. These systemic challenges also increased neuronal apoptosis in the brains of ME7 animals. Thus, both central and peripheral inflammation can exacerbate local brain inflammation and neuronal death. The finding that a single acute systemic inflammatory event can induce neuronal death in the CNS has implications for therapy in neurodegenerative diseases.

show abstract

Section: Mechanisms and Implicationsmentioning

confidence: 85%

Central and Systemic Endotoxin Challenges Exacerbate the Local Inflammatory Response and Increase Neuronal Death during Chronic Neurodegeneration

Cunningham¹,

Wilcockson²,

Campion³

et al. 2005

J. Neurosci.

673

575

View full text Add to dashboard Cite

show abstract

“…The relationship between immune markers, such as IL-1β, IL-6, IL-8, TNF-α, and CRP, and cognitive functioning has been described in several population studies on older persons (Singh and Newman 2011;Holmes et al 2003;Baune et al 2008;Weaver et al 2002;Bruunsgaard et al 1999;Dik et al 2005;van Exel et al 2003).…”

mentioning

confidence: 99%

Significance of serum immune markers in identification of global functional impairment in the oldest old: cross-sectional results from the BELFRAIL study

Adriaensen

Matheï

Pottelbergh

et al. 2013

AGE

View full text Add to dashboard Cite

The large burden and coexistence of physical disability, cognitive impairment, and depression in the oldest old makes summary markers of global functioning of great value, allowing for risk stratification. Inflammation may be a common underlying cause or represents a final common pathway. The present study investigated the association between elevated serum inflammatory markers and global functioning and its underlying aspects. A representative sample of 415 communitydwelling elderly subjects participating in the BELFRAIL study, with a mean age of 85 years, was included in the present analysis. Data on physical performance, dependence, and mental aspects of functioning and serum levels of 15 inflammatory proteins, including cytokines, chemokines, and acute-phase proteins, were assessed. Interleukin (IL)-6 was negatively associated with global functioning (odds ratio (OR) 4.35). The odds ratios for C-reactive protein (CRP) (OR 2.37) and the combined score of IL-6 and CRP (OR 2.59) were lower or not significant. IL-6 was significantly associated with physical dependence and cognitive function, and only a highly elevated serum level was associated with physical performance. Physical dependence was associated with a highly elevated CRP serum level. The proportion of functionally impaired older persons with elevated IL-6 was 81.93 %, giving a low positive predictive value (0.38), but a high negative predictive value (0.87). So, IL-6 is strongly associated with global functioning and all of the individual aspects of functioning, except suspected depression, in communitydwelling persons 80 years and older.

show abstract

“…A central tenet of the inflammatory hypothesis is that peripheral processes alter brain inflammation. Studies have shown that peripheral infections can hasten the onset and progression of AD although the mechanisms are not well understood [41,83]. Periodontal disease (PD) is a common, chronic, peripheral infectious disease that has been linked to other systemic inflammatory conditions.…”

Section: Introductionmentioning

confidence: 99%

Alzheimer's Disease and Peripheral Infections: The Possible Contribution from Periodontal Infections, Model and Hypothesis

Kamer¹,

Dasanayake²,

Craig³

et al. 2008

JAD

153

View full text Add to dashboard Cite

Abstract. Alzheimer's disease (AD) affects approximately 4.5 million people in the U.S. and this number will increase as the population ages and the life-span increases. Therefore, of paramount importance is identifying mechanisms and factors that affect the risk of developing AD. The etiology and pathogenic mechanisms for AD have not been defined, although inflammation within the brain is thought to play a role. Consistent with this hypothesis, studies suggest that peripheral infections contribute to the inflammatory state of the central nervous system. Periodontitis is a prevalent, persistent peripheral infection associated with gram negative, anaerobic bacteria that are capable of exhibiting localized and systemic infections in the host. This review offers a hypothetical link between periodontitis and AD and will present possible mechanistic links between periodontitis related inflammation and AD. It will review the pathogenesis of periodontitis and the mechanisms by which periodontal infections may affect the onset and progression of AD. Since periodontitis is a treatable condition, it may be a readily modifiable risk factor for AD.

show abstract

Systemic infection, interleukin 1beta, and cognitive decline in Alzheimer's disease

Cited by 303 publications

References 8 publications

Central and Systemic Endotoxin Challenges Exacerbate the Local Inflammatory Response and Increase Neuronal Death during Chronic Neurodegeneration

Central and Systemic Endotoxin Challenges Exacerbate the Local Inflammatory Response and Increase Neuronal Death during Chronic Neurodegeneration

Significance of serum immune markers in identification of global functional impairment in the oldest old: cross-sectional results from the BELFRAIL study

Alzheimer's Disease and Peripheral Infections: The Possible Contribution from Periodontal Infections, Model and Hypothesis

Contact Info

Product

Resources

About