TNFα plus IFNγ induce the production of Alzheimer β‐amyloid peptides and decrease the secretion of APPs

Blasko, Imrich; Marx, Florentine; Steiner, Eberhard; Hartmann, Tobias; Grubeck‐Loebenstein, B.

doi:10.1096/fasebj.13.1.63

Cited by 270 publications

(188 citation statements)

References 30 publications

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“…In the current long-term study NA depletion also elevated the amyloid plaque load in affected projection areas. Although this increase might be secondary to the elevated inflammation state, which could increase A␤ generation (Blasko et al, 1999;Sastre et al, 2003), it seems possible as well that it occurs by an independent, more direct mechanism. In this case the increase in amyloid may contribute to increased inflammation.…”

Section: Discussionmentioning

confidence: 99%

Locus Ceruleus Degeneration Promotes Alzheimer Pathogenesis in Amyloid Precursor Protein 23 Transgenic Mice

et al. 2006

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Locus ceruleus (LC) degeneration and loss of cortical noradrenergic innervation occur early in Alzheimer's disease (AD). Although this has been known for several decades, the contribution of LC degeneration to AD pathogenesis remains unclear. We induced LC degeneration with N-(2-chloroethyl)-N-ethyl-bromo-benzylamine (dsp4) in amyloid precursor protein 23 (APP23) transgenic mice with a low amyloid load. Then 6 months later the LC projection areas showed a robust elevation of glial inflammation along with augmented amyloid plaque deposits. Moreover, neurodegeneration and neuronal loss significantly increased. Importantly, the paraventricular thalamus, a nonprojection area, remained unaffected. Radial arm maze and social partner recognition tests revealed increased memory deficits while high-resolution magnetic resonance imaging-guided micro-positron emission tomography demonstrated reduced cerebral glucose metabolism, disturbed neuronal integrity, and attenuated acetylcholinesterase activity. Nontransgenic mice with LC degeneration were devoid of these alterations. Our data demonstrate that the degeneration of LC affects morphology, metabolism, and function of amyloid plaque-containing higher brain regions in APP23 mice. We postulate that LC degeneration substantially contributes to AD development.

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Section: Discussionmentioning

confidence: 99%

Locus Ceruleus Degeneration Promotes Alzheimer Pathogenesis in Amyloid Precursor Protein 23 Transgenic Mice

et al. 2006

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“…Additionally, this mechanism may be causal to many psychiatric and neurological diseases [148,167,168]. In the context of AD pathogenesis, the central pro-inflammatory cytokines have been shown to enhance the phosphorylation of tau or production of amyloid beta peptide and potentiate the neurodegeneration process [148,169,170].…”

Section: Proinflammatory Cytokinesmentioning

confidence: 99%

Metabolic Risk Factors of Sporadic Alzheimer's Disease: Implications in the Pathology, Pathogenesis and Treatment

Chakrabarti¹,

Khemka²,

Banerjee³

et al. 2015

Aging and disease

107

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Alzheimer's disease (AD), the major cause of dementia among the elderly world-wide, manifests in familial and sporadic forms, and the latter variety accounts for the majority of the patients affected by this disease. The etiopathogenesis of sporadic AD is complex and uncertain. The autopsy studies of AD brain have provided limited understanding of the antemortem pathogenesis of the disease. Experimental AD research with transgenic animal or various cell based models has so far failed to explain the complex and varied spectrum of AD dementia. The review, therefore, emphasizes the importance of AD related risk factors, especially those with metabolic implications, identified from various epidemiological studies, in providing clues to the pathogenesis of this complex disorder. Several metabolic risk factors of AD like hypercholesterolemia, hyperhomocysteinemia and type 2 diabetes have been studied extensively both in epidemiology and experimental research, while much less is known about the role of adipokines, proinflammatory cytokines and vitamin D in this context. Moreover, the results from many of these studies have shown a degree of variability which has hindered our understanding of the role of AD related risk factors in the disease progression. The review also encompasses the recent recommendations regarding clinical and neuropathological diagnosis of AD and brings out the inherent uncertainty and ambiguity in this area which may have a distinct impact on the outcome of various population-based studies on AD-related risk factors.

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“…A cytokine array study was assessed in order to detect APP expression and interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) or interferon (INF)-γ were found to increase the levels of APP. It was also shown that cytokines have a direct link in the upregulation of β-secretase [41] (the rate-limiting and necessary enzyme to synthetize Aβ deposits) and Aβ formation [40] . Kitazawa and colleagues described that microglia became activated in a progressive and age-dependent manner in the brain of a transgenic AD model (3xTg-AD) mice [42] .…”

Section: Chronic Stress Is a Risk Factor For The Development Of Neuromentioning

confidence: 99%

Stress and Inflammation: A Detrimental Combination in the Development of Neurodegenerative Disease.

Pablos

Espinosa-Oliva

Sarmiento

et al. 2014

Inflamm Cell Signal

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Chronic stress accelerates the appearance of some neurodegenerative disorders, such as Alzheimer's disease and Parkinson´s disease. On this review we firstly, describe some human epidemiological studies that highlight the possibility that chronic stress could increase the incidence or the rate of incidence of Alzheimer's disease and Parkinson´s disease. Secondly, we discuss the important role of inflammation in the progression and development of these neurodegenerative diseases. Finally, we try to justify the relationship between stress and inflammation with some experimental data. This work strongly suggests that chronic stress could be considered a key factor for the development of neurodegenerative diseases through microglial activation. Keywords: stress; inflammation; neurodegenerative diseasesTo cite this article: Rocío M. de Pablos, et al. Stress and inflammation: a detrimental combination in the development of neurodegenerative disease. Inflamm Cell Signal 2014; 1: e182. doi: 10.14800/ics.182.Copyright: © 2014 The Authors. Licensed under a Creative Commons Attribution 4.0 International License which allows users including authors of articles to copy and redistribute the material in any medium or format, in addition to remix, transform, and build upon the material for any purpose, even commercially, as long as the author and original source are properly cited or credited. IntroductionStress could be simply defined as any disruption of homeostasis, whereas 'stressor' would be any of the myriads of internal or external challenges that cause this disruption [1][2][3][4] . Disturbed homeostasis initiates a series of events called the stress response or cascade; this wellchoreographed response will involve the hypothalamic pituitary adrenal (HPA) axis that is in charge to restore homeostasis. Stress is a condition of human experience and an important factor in the onset of various diseases [5] . In general, it is considered that stress is not reduced only to the dramatic stressful events in our lives but rather to all those little daily problems that are capable of raising the activity of physiological systems sufficiently to cause a wear.Exposure to stressful situations triggers the activation of two systems: the sympatho-adreno-medullary system and the HPA system [6] . The first leads to raise the levels of circulating adrenaline whereas the second run the release of corticosteroid hormones from the adrenal cortex. Corticosteroid hormones have the ability to cross the blood brain barrier owing to their lipophilic properties and 2014; 1: e182. doi: 10.14800/ics.182; © 2014 by Rocío M. de Pablos, et al. http://www.smartscitech.com/index.php/ics Page 2 of 8 interact with to two classes of receptors: mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) [7] . MR and GR have different affinity for corticosterone, whilst MR have great affinity GR show less attraction with the endogenous hormone. They also differ in their distribution; MR are located mainly within limbic regions (eg. amygdala and h...

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TNFα plus IFNγ induce the production of Alzheimer β‐amyloid peptides and decrease the secretion of APPs

Cited by 270 publications

References 30 publications

Locus Ceruleus Degeneration Promotes Alzheimer Pathogenesis in Amyloid Precursor Protein 23 Transgenic Mice

Locus Ceruleus Degeneration Promotes Alzheimer Pathogenesis in Amyloid Precursor Protein 23 Transgenic Mice

Metabolic Risk Factors of Sporadic Alzheimer's Disease: Implications in the Pathology, Pathogenesis and Treatment

Stress and Inflammation: A Detrimental Combination in the Development of Neurodegenerative Disease.

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