APOE epsilon‐4 allele and cytokine production in Alzheimer's disease

Olgiati, Paolo; Politis, Antonis; Malitas, Petros; Albani, Diego; Dusi, Sabrina; Polito, Letizia; Mauro, Stefania De; Zisaki, Aikaterini; Piperi, Christina; Stamouli, Evangelia; Mailis, Antonis; Batelli, Sara; Forloni, Gianluigi; Ronchi, Diana De; Kalofoutis, Anastasios; Liappas, Ioannis; Serretti, Alessandro

doi:10.1002/gps.2344

Cited by 28 publications

(20 citation statements)

References 51 publications

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“…Animal models have shown the influence of APOE alleles on proinflammatory cytokine (TNF-alpha; IL-6; IL-1) expression and sepsis [154–156]. Recently, we have reported an association between APOE alleles and IL-1beta levels in patients with AD [157]. Apolipoprotein E has a protective effect against apoptosis which is significantly reduced in the presence of the pathogenic epsilon 4 isoform [158].…”

Section: Discussionmentioning

confidence: 99%

Genetics of Late‐Onset Alzheimer′s Disease: Update from the Alzgene Database and Analysis of Shared Pathways

Olgiati

Politis

Papadimitriou

et al. 2011

International Journal of Alzheimer's Disease

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The genetics of late-onset Alzheimer's disease (LOAD) has taken impressive steps forwards in the last few years. To date, more than six-hundred genes have been linked to the disorder. However, only a minority of them are supported by a sufficient level of evidence. This review focused on such genes and analyzed shared biological pathways. Genetic markers were selected from a web-based collection (Alzgene). For each SNP in the database, it was possible to perform a meta-analysis. The quality of studies was assessed using criteria such as size of research samples, heterogeneity across studies, and protection from publication bias. This produced a list of 15 top-rated genes: APOE, CLU, PICALM, EXOC3L2, BIN1, CR1, SORL1, TNK1, IL8, LDLR, CST3, CHRNB2, SORCS1, TNF, and CCR2. A systematic analysis of gene ontology terms associated with each marker showed that most genes were implicated in cholesterol metabolism, intracellular transport of beta-amyloid precursor, and autophagy of damaged organelles. Moreover, the impact of these genes on complement cascade and cytokine production highlights the role of inflammatory response in AD pathogenesis. Gene-gene and gene-environment interactions are prominent issues in AD genetics, but they are not specifically featured in the Alzgene database.

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Section: Discussionmentioning

confidence: 99%

Genetics of Late‐Onset Alzheimer′s Disease: Update from the Alzgene Database and Analysis of Shared Pathways

Olgiati

Politis

Papadimitriou

et al. 2011

International Journal of Alzheimer's Disease

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“…Among AD patients, those with the apoE4 allele had greater baseline and stimulated levels of IL-1β (Olgiati et al, 2010). ApoE co-localizes with microglia around Aβ plaques (Liu et al, 2013), and apoE4 mice have greater microgliosis and astrogliosis in response to Aβ than do apoE3 mice (Belinson and Michaelson, 2009).…”

Section: Mechanisms Underlying Sex Differences In Obesity and Alzhmentioning

confidence: 99%

Obesity and sex interact in the regulation of Alzheimer's disease

Moser

Pike

2016

Neuroscience & Biobehavioral Reviews

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, for which a number of genetic, environmental, and lifestyle risk factors have been identified. A significant modifiable risk factor is obesity in mid-life. Interestingly, both obesity and AD exhibit sex differences and are regulated by sex steroid hormones. Accumulating evidence suggests interactions between obesity and sex in regulation of AD risk, although the pathways underlying this relationship are unclear. Inflammation and the E4 allele of apolipoprotein E have been identified as independent risk factors for AD and both interact with obesity and sex steroid hormones. We review the individual and cooperative effects of obesity and sex on development of AD and examine the potential contributions of apolipoprotein E, inflammation, and their interactions to this relationship.

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“…It is important to underscore, however, that additional cross-sectional studies report no significant correlations between inflammation and MMSE (Olgiati et al, 2010; Ozturk et al, 2007; Popp et al, 2009), positive correlations (Kim et al, 2008; Sala et al, 2003), or report associations only with specific cytokines (e.g., IL-1 levels, but not TNF-α) (Tarkowski et al, 2003). For example, Sala et al (2003) reported a positive relationship between MMSE and three pro-inflammatory markers, including IL-1, IL-6, and TNF-α, and interpreted these findings as preliminary evidence for downregulation of inflammation in late clinical stages of the disease.…”

Section: Inflammation and Neurodegenerative Diseasementioning

confidence: 99%

“…While isolated reports indicate a negative correlation between inflammatory mediators and episodic memory (Forlenza et al, 2009), there is a dearth of information regarding how inflammation might associate or interact with particular cognitive domains in AD. Recent studies have addressed other neurobehavioral correlates of inflammation, and reported significant associations between cytokine levels and neuropsychiatric symptoms (Olgiati et al, 2010; Ozturk et al, 2007); in particular, TNF-α levels have been shown to positively correlate with symptoms associated with sickness behavior (Holmes et al, 2011), including depression, anxiety, agitation, and apathy on the Neuropsychiatric Inventory (NPI) in Alzheimer’s disease. However, there continues to be a lack of specificity in the literature regarding how and to what degree inflammation relates to specific cognitive and neurobehavioral processes.…”

Section: Inflammation and Neurodegenerative Diseasementioning

confidence: 99%

Inflammation and clinical presentation in neurodegenerative disease: a volatile relationship

Bettcher

Kramer

2013

Neurocase

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A proposed immune mechanism that potentially modifies or exacerbates neurodegenerative disease presentation in older adults has received considerable attention in the past decade, with recent studies demonstrating a strong link between pro-inflammatory markers and neurodegeneration. The overarching aim of the following review is to synthesize recent research that supports a possible relationship between inflammation and clinical features of neurodegenerative diseases, including risk of development, cognitive and clinical correlates, and progression of the specified diseases. Specific emphasis is placed on providing a temporal context for the association between inflammation and neurodegeneration.

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APOE epsilon‐4 allele and cytokine production in Alzheimer's disease

Cited by 28 publications

References 51 publications

Genetics of Late‐Onset Alzheimer′s Disease: Update from the Alzgene Database and Analysis of Shared Pathways

Genetics of Late‐Onset Alzheimer′s Disease: Update from the Alzgene Database and Analysis of Shared Pathways

Obesity and sex interact in the regulation of Alzheimer's disease

Inflammation and clinical presentation in neurodegenerative disease: a volatile relationship

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