Inflammatory processes induce beta-amyloid precursor protein changes in mouse brain.

Brugg, Bernard; Dubreuil, Yolande Lemaigre; Huber, G.; Wollman, Emmanuelle E.; Delhaye‐Bouchaud, Nicole; Mariani, Jean

doi:10.1073/pnas.92.7.3032

Cited by 181 publications

(105 citation statements)

References 43 publications

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“…Systemic administration of LPS to rodents causes upregulation of COX2 in brain perivascular and endothelial cells (Elmquist et al, 1997;Yermakova and O'Banion, 2001) and alters the expression or processing of APP or both. It also accelerates the generation of Aβ42 in transgenic mice that overexpress the Swedish variant of APP695 (Sheng et al, 2003) and increases the abundance of APP751 (Brugg et al, 1995). LPS could cause these effects by several mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Brain Inflammation and Alzheimer's-Like Pathology in Individuals Exposed to Severe Air Pollution

et al. 2004

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Air pollution is a complex mixture of gases (e.g., ozone), particulate matter, and organic compounds present in outdoor and indoor air. Dogs exposed to severe air pollution exhibit chronic inflammation and acceleration of Alzheimer's-like pathology, suggesting that the brain is adversely affected by pollutants. We investigated whether residency in cities with high levels of air pollution is associated with human brain inflammation. Expression of cyclooxygenase-2 (COX2), an inflammatory mediator, and accumulation of the 42-amino acid form of β-amyloid (Aβ42), a cause of neuronal dysfunction, were measured in autopsy brain tissues of cognitively and neurologically intact lifelong residents of cities having low (n:9) or high (n:10) levels of air pollution. Genomic DNA apurinic/apyrimidinic sites, nuclear factor-κB activation and apolipoprotein E genotype were also evaluated. Residents of cities with severe air pollution had significantly higher COX2 expression in frontal cortex and hippocampus and greater neuronal and astrocytic accumulation of Aβ42 compared to residents in low air pollution cities. Increased COX2 expression and Aβ42 accumulation were also observed in the olfactory bulb. These findings suggest that exposure to severe air pollution is associated with brain inflammation and Aβ42 accumulation, two causes of neuronal dysfunction that precede the appearance of neuritic plaques and neurofibrillary tangles, hallmarks of Alzheimer's disease.

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Section: Discussionmentioning

confidence: 99%

Brain Inflammation and Alzheimer's-Like Pathology in Individuals Exposed to Severe Air Pollution

et al. 2004

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“…It has been shown previously that peripheral stimulation with LPS induced a transient increase in inflammatory cytokine mRNAs, and changes in APP isoforms in the brains of mice [6]. In addition, others have shown that bacterial LPS infused into the rat brain induces an inflammatory response as indicated by microglial reactivity and cytokine expression, characteristic of inflammation in the AD brain [14].…”

Section: Amyloid Depositionmentioning

confidence: 93%

Chlamydia pneumoniae induces Alzheimer-like amyloid plaques in brains of BALB/c mice

Little

Hammond

MacIntyre

et al. 2004

Neurobiology of Aging

206

197

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Amyloid deposits resembling plaques found in Alzheimer's disease (AD) brains were formed in the brains of non-transgenic BALB/c mice following intranasal infection with Chlamydia pneumoniae. The mice were infected at 3 months of age with C. pneumoniae isolated from an AD brain. Infection was confirmed by light and electron microscopy in olfactory tissues of the mice. C. pneumoniae was still evident in these tissues 3 months after the initial infection indicating that a persistent infection had been established. Amyloid beta (A␤) 1-42 immunoreactive deposits were identified in the brains of infected BALB/c mice up to 3 months post-infection with the density, size, and number of deposits increasing as the infection progressed. A subset of deposits exhibited thioflavin-s labeling. Intracellular A␤1-42 labeling was observed in neuronal cells. Experimental induction of amyloid deposition in brains of non-transgenic BALB/c mice following infection with C. pneumoniae may be a useful model for furthering our understanding of mechanisms, linked to infection, involved in the initiation of the pathogenesis of sporadic AD.

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“…Stimuli that lead to microglial priming, such as systemic infections and elevated plasma IL-1β/TNF-α, are correlated with accelerated cognitive decline in Alzheimer's disease patients (1,2). In Alzheimer's disease models, repeated LPS challenges exacerbate tau pathology (3), inflammation (4), and amyloid deposition (5). In prion disease models, microglial priming is evident even in the preclinical stage, and LPS challenge exacerbates neuronal death, induces acute cognitive impairment, and accelerates disease progression (6)(7)(8).…”

mentioning

confidence: 99%

C3-dependent mechanism of microglial priming relevant to multiple sclerosis

Ramaglia¹,

Hughes²,

Donev³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

132

102

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Microglial priming predisposes the brain to neurodegeneration and affects disease progression. The signal to switch from the quiescent to the primed state is unknown. We show that deleting the C3 convertase regulator complement receptor 1-related protein y (Crry) induces microglial priming. Mice that were double-knockout for Crry and either C3 or factor B did not show priming, demonstrating dependence on alternative pathway activation. Colocalization of C3b/ iC3b and CR3 implicated the CR3/iC3b interaction in priming. Systemic lipopolysaccharide challenge overactivated primed microglia with florid expression of proinflammatory molecules, which were blocked by complement inhibition. Relevance for neurodegenerative disease is exemplified by human multiple sclerosis (MS) and by experimental autoimmune encephalomyelitis (EAE), a model of MS. In human MS, microglial priming was evident in perilesional white matter, in close proximity to C3b/iC3b deposits. EAE was accelerated and exacerbated in Crry-deficient mice, and was dependent on C activation. In summary, C3-dependent microglial priming confers susceptibility to other challenges. Our observations are relevant to progression in MS and other neurological diseases exacerbated by acute insults.

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Inflammatory processes induce beta-amyloid precursor protein changes in mouse brain.

Cited by 181 publications

References 43 publications

Brain Inflammation and Alzheimer's-Like Pathology in Individuals Exposed to Severe Air Pollution

Brain Inflammation and Alzheimer's-Like Pathology in Individuals Exposed to Severe Air Pollution

Chlamydia pneumoniae induces Alzheimer-like amyloid plaques in brains of BALB/c mice

C3-dependent mechanism of microglial priming relevant to multiple sclerosis

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