Resolution of inflammation is altered in Alzheimer's disease

Wang, Xiuzhe; Zhu, Mingqin; Hjorth, Erik; Cortés-Toro, Veronica; Eyjolfsdottir, Helga; Graff, Caroline; Nennesmo, Inger; Palmblad, Jan; Eriksdotter, Maria; Sambamurti, Kumar; Fitzgerald, Jonathan M.; Serhan, Charles N.; Granholm, Ann‐Charlotte; Schultzberg, Marianne

doi:10.1016/j.jalz.2013.12.024

Cited by 243 publications

(303 citation statements)

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“…Upon binding to their specifi c receptors, SPMs downregulate proinfl ammatory signals and promote the healing process of the tissue ( 11 ). Recent studies have indicated that resolution of infl ammation is disturbed in AD ( 12,13 ) and AD-related models (14)(15)(16). Treatment with one of the SPMs, lipoxin A 4 (LXA 4 ), has been demonstrated to rescue synaptic loss and reduce AD-like pathologies in transgenic AD mouse models ( 17,18 ).…”

Section: Pbmc Preparation and Ex Vivo Experimentsmentioning

confidence: 99%

“…Interestingly, A ␤ 40 was shown to decrease the production of the anti-infl ammatory cytokine interleukin (IL)-10 by PBMCs from AD patients ( 28 ). IL-10 has been shown to be decreased in the hippocampus of AD patients ( 13 ). Thus, the effect of A ␤ 40 on PBMCs indicates its ability to impair anti-infl ammatory signaling in a way that is relevant to AD, in addition to its well-known proinfl ammatory properties.…”

Section: Pbmc Preparation and Ex Vivo Experimentsmentioning

confidence: 99%

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Effects of n-3 FA supplementation on the release of proresolving lipid mediators by blood mononuclear cells: the OmegAD study

Wang

Hjorth

Vedin

et al. 2015

Journal of Lipid Research

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This article is available online at http://www.jlr.org Many diseases of the brain display signs of infl ammation, including Alzheimer's disease (AD), the most common type of dementia. The association between infl ammation and AD is evidenced from many different disciplines of research. Postmortem studies have revealed increased levels of proinfl ammatory cytokines in the AD brain ( 1-3 ), particularly around the amyloid plaques, and further support is provided by analysis of clinical samples from AD patients, including elevated proinfl ammatory markers in cerebrospinal fl uid (CSF) ( 4 ) and plasma/serum ( 5-7 ) samples. Epidemiological studies have shown that longterm use of nonsteroidal anti-infl ammatory drugs (NSAIDs) confers reduced prevalence of AD ( 8 ). However, prospective clinical trials based on NSAIDs have not been successful in reducing the cognitive decline in AD ( 8, 9 ).Consumption of PUFAs, especially the n-3 FAs DHA and EPA, is well known for benefi cial effects in the regulation of infl ammation ( 10 ). PUFAs can modulate the infl ammatory response by changing cell membrane fl uidity and composition, leading to effects on the function of receptors, and the conductance of ion channels involved in immune activation. In recent years, the concept of resolution of infl ammation has received attention due to the discovery of specialized proresolving mediators (SPMs). SPMs are lipid mediators (LMs) derived from PUFAs and play a key role in resolution, in which the tissue is restored by removal of cellular and molecular debris, and regeneration/ Abstract Specialized proresolving mediators (SPMs) induce resolution of infl ammation. SPMs are derivatives of n-3 and n-6 PUFAs and may mediate their benefi cial effects. It is unknown whether supplementation with PUFAs infl uences the production of SPMs. Alzheimer's disease (AD) is associated with brain infl ammation and reduced levels of SPMs. The OmegAD study is a randomized, double-blind, and placebo-controlled clinical trial on AD patients, in which placebo or a supplement of 1.7 g DHA and 0.6 g EPA was taken daily for 6 months. Plasma levels of arachidonic acid decreased, and DHA and EPA levels increased after 6 months of n-3 FA treatment. Peripheral blood mononuclear cells (PBMCs) were obtained before and after the trial. Analysis of the culture medium of PBMCs incubated with amyloid-␤ 1-40 showed unchanged levels of the SPMs lipoxin A 4 and resolvin D1 in the group supplemented with n-3 FAs, whereas a decrease was seen in the placebo group. The changes in SPMs showed correspondence to cognitive changes. Changes in the levels of SPMs were positively correlated to changes in transthyretin. We conclude that supplementation with n-3 PUFAs for 6 months prevented a reduction in SPMs released from PBMCs of AD patients, which was associated with changes in cognitive function.

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Section: Pbmc Preparation and Ex Vivo Experimentsmentioning

confidence: 99%

Section: Pbmc Preparation and Ex Vivo Experimentsmentioning

confidence: 99%

Effects of n-3 FA supplementation on the release of proresolving lipid mediators by blood mononuclear cells: the OmegAD study

Wang

Hjorth

Vedin

et al. 2015

Journal of Lipid Research

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“…To support this notion, while proinflammatory stimuli such as LPS promoted resolvin pathways activation in microglia, Aβ42 had an opposite or insignificant effect suggesting that pro-resolutive pathways are impaired in AD (Zhu et al, 2015). This is further substantiated by the observation that the lipoxin A4 (LXA4) level is decreased in postmortem brain tissue and cerebrospinal fluid samples from AD patients (Wang et al, 2015b). Very recently, it was shown that upon Aβ40 exposure, peripheral blood mononuclear cells from AD patients secreted less LXA4 and RvD1 together with the disease progression.…”

Section: How Do N-3 Pufa Mechanisms Control Neuroinflammation?mentioning

confidence: 94%

N-3 PUFAs and neuroinflammatory processes in cognitive disorders

Leyrolle

Layé

Nadjar

2016

OCL

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-With the ageing population and increased cases of neurodegenerative diseases, there is a crucial need for the development of new nutritional approaches to prevent and delay the onset of cognitive decline. Neuroinflammatory processes contribute to neuronal damage that underpins neurodegenerative disorders. Growing evidence sheds light on the use of dietary n-3 long chain polyunsaturated fatty acids to improve cognitive performances and reduce the neuroinflammatory responses occurring with age and neurodegenerative pathologies. This review will summarise the most recent information related to the impact and mechanisms underlying the neuroinflammatory processes in cognitive disorders. We will also discuss the mechanisms underlying n-3 polyunsaturated fatty acids effect on neuroinflammation and memory decline.Keywords: Neuroinflammation / microglia / n-3 polyunsaturated fatty acids / cognitive disorders / Alzheimer disease Résumé -Acides gras polyinsaturés de la famille des oméga 3, processus neuroinflammatoires et troubles cognitifs. Le développement d'approches nutritionnelles pertinentes pour prévenir et retarder l'apparition du déclin cognitif est un enjeu important, compte tenu du vieillissement de la population et de l'augmentation de l'incidence des maladies neurodégénératives. Les processus neuro-inflammatoires contribuent aux mécanismes neuropathologiques impliqués dans les troubles neurodégénératifs et de la cognition. Des données récentes indiquent l'importance des acides gras polyinsaturés n-3 alimentaires dans le maintien des performances mnésiques et la régulation de la neuroinflammation liée à l'âge ou à la maladie d'Alzheimer. Dans cette revue, seront présentées des données récentes sur les liens existants entre le statut nutritionnel en acides gras polyinsaturés n-3, les processus neuro-inflammatoires et les troubles cognitifs associés, ainsi que les mécanismes qui pourraient être impliqués dans les effets protecteurs de ces acides gras.

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“…A defective regulation of inflammatory responses in AD brains has been recently found; such impairment also correlated with patient cognitive performances [29]. Brain inflammation markers were also found elevated in cerebral spinal fluid (CSF) from preclinical AD [30].…”

Section: Brain Immunity and Admentioning

confidence: 97%

Individual Risk Detection of Developing Cognitive Decline and Dementia in Adults with Down’s Syndrome

Licastro¹,

Porcellini²

2017

Down Syndr Chr Abnorm

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IntroductionAlzheimer's disease (AD) is the leading cause of dementia in the elderly. Prevalence and incidence of this type of dementia is increasing and extensive research has focused on AD pathogenetic mechanisms to find effective preventive procedures and therapeutic drugs. However, no therapy is available. Therefore, focusing upon diverse aspects of the disease in order to discover new therapeutic strategies appears to be relevant for patients. Moreover, new approaches to the disease's pathogenesis may open innovative prevention opportunities for the elderly or other groups of people without manifest cognitive alterations, but with increased risk of developing dementia.Brain amyloid deposits and intra neuronal neurofibrillary tangles (NFTs) have been suggested as inducers of the disease [1,2]. However, these neuropathological alterations are often also present in the brain of elderly without cognitive alterations or AD pathology [3]. Therefore, it is uncertain whether amyloid or other proteinaceous brain depositions might be causatively linked to AD.The biological role of the amyloid precursor protein (APP) and its proteolytic derivatives (A-beta peptide) in normal brain is still uncertain [4]. However, recent data showed that A-beta peptide is an anti-microbial factor [5]. A recent study reported that the A-beta peptide showed an in vitro anti-virus activity [6]. Therefore, A-beta peptides may play multiple roles in human brain and contribute to antimicroorganism responses.As we elsewhere discussed, genetic data from four genome wide association (GWA) studies on AD [7][8][9] suggested that persistent virus infections may be potentially associated with the age related cognitive decline. In fact, this specific genetic signature may predispose to AD by affecting the individual susceptibility to virus infections [7] during the age associated decline of immune competence. Adults with Down's syndrome (DS) o trisomy of chromosome 21show an elevated risk of cognitive decline and dementia with advancing age. The over expression of the APP gene on the chromosome 21 may lead to an early amyloid deposition in DS brains and be a susceptibility factor for AD [10].Middle age people with DS also show increased tangle brain deposition, neuronal loss and neuro-inflammation along with cerebrovascular pathology [10]. All these factors might accelerate brain aging in DS. A dramatic increase in life expectancy, coupled with a significant reduction in early mortality, has led to a substantial increment in the number of DS subjects reaching old age. This demographic picture parallels increased incidence and prevalence of the age related degenerative diseases in persons with DS.Chronic inflammation is associated with the pathogenesis of most chronic degenerative diseases. In fact, a relevant inflammatory component is always associated with AD, autoimmune diseases, diabetes, atherosclerosis, sarcopenia and cancer. It is of interest that increased levels of circulating inflammatory mediators may be secondary to impaired cytokine resp...

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Resolution of inflammation is altered in Alzheimer's disease

Cited by 243 publications

References 47 publications

Effects of n-3 FA supplementation on the release of proresolving lipid mediators by blood mononuclear cells: the OmegAD study

Effects of n-3 FA supplementation on the release of proresolving lipid mediators by blood mononuclear cells: the OmegAD study

N-3 PUFAs and neuroinflammatory processes in cognitive disorders

Individual Risk Detection of Developing Cognitive Decline and Dementia in Adults with Down’s Syndrome

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