The CC genotype of transforming growth factor-β1 increases the risk of late-onset Alzheimer's disease and is associated with AD-related depression

Caraci, Filippo; Bosco, Paolo; Signorelli, Maria; Spada, Rosario S.; Cosentino, F.; Toscano, Giuseppe; Bonforte, Cinzia; Muratore, Stefano; Prestianni, Giuseppina; Panerai, Simonetta; Giambirtone, Mariaconcetta; Gulotta, Eleonora; Romano, Carmelo; Salluzzo, Maria Grazia; Nicoletti, Ferdinando; Copani, Agata; Drago, Filippo; Aguglia, Eugenio; Ferri, Raffaele

doi:10.1016/j.euroneuro.2011.08.006

Cited by 49 publications

(31 citation statements)

References 74 publications

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“…Both the ?10 T/C and -509 C/T polymorphisms have been suggested to influence TGFB1 gene transcription and TGF-b1 protein expression [47,125], and a series of studies has explored their interactions with AD risk. The ?10 T/C polymorphism was associated with increased AD risk in studies by Arosio et al and Caraci et al [43,44], and the -509 C/T polymorphism exhibited the same association in a study by Luedecking et al [47]. Moreover, patients with mild cognitive impairment carrying the ?10 C allele had an increased risk of developing AD over a 4-year follow-up conducted by Arosio et al [43].…”

Section: Tgfb1mentioning

confidence: 63%

“…However, inconsistent results have been reported in the majority of studies conducted in various populations [126], and a negative association has been further supported by a recent metaanalysis [126]. No positive results have been obtained for the other SNPs in TGFB1 [43,44,46,73,[127][128][129], so it remains controversial whether TGFB1 polymorphisms influence AD risk.…”

Section: Tgfb1mentioning

confidence: 96%

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Inflammatory Cytokines and Alzheimer’s Disease: A Review from the Perspective of Genetic Polymorphisms

2016

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Neuroinflammatory processes are a central feature of Alzheimer's disease (AD) in which microglia are over-activated, resulting in the increased production of proinflammatory cytokines. Moreover, deficiencies in the antiinflammatory system may also contribute to neuroinflammation. Recently, advanced methods for the analysis of genetic polymorphisms have further supported the relationship between neuroinflammatory factors and AD risk because a series of polymorphisms in inflammation-related genes have been shown to be associated with AD. In this review, we summarize the polymorphisms of both pro-and anti-inflammatory cytokines related to AD, primarily interleukin-1 (IL-1), IL-6, tumor necrosis factor alpha, IL-4, IL-10, and transforming growth factor beta, as well as their functional activity in AD pathology. Exploration of the relationship between inflammatory cytokine polymorphisms and AD risk may facilitate our understanding of AD pathogenesis and contribute to improved treatment strategies.

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Section: Tgfb1mentioning

confidence: 63%

Section: Tgfb1mentioning

confidence: 96%

Inflammatory Cytokines and Alzheimer’s Disease: A Review from the Perspective of Genetic Polymorphisms

2016

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“…The RCTs conducted on patients with mild cognitive impairment or AD revealed poor efficacy of omega-3 PUFA in ameliorating the depressive symptoms. It has been reported that molecular mechanisms and pathways that underlie the pathogenesis of depression (i.e., impairment in the signaling of some neurotrophins such as Transforming-Growth-Factor-β1 and Brain-derived-neurotrophic-factor) are also involved in the pathogenesis of AD [114], [115], thus the omega-3 PUFA supplementation may not be the optimal pharmacological approach for this specific group of patients [116]–[118]. The two trials (including different dosages) conducted on schizophrenic patients with persistent ongoing symptoms resulted in limited effects of the omega-3 PUFA on patients’ affective states.…”

Section: Discussionmentioning

confidence: 99%

Role of Omega-3 Fatty Acids in the Treatment of Depressive Disorders: A Comprehensive Meta-Analysis of Randomized Clinical Trials

et al. 2014

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BackgroundDespite omega-3 polyunsaturated fatty acids (PUFA) supplementation in depressed patients have been suggested to improve depressive symptomatology, previous findings are not univocal.ObjectivesTo conduct an updated meta-analysis of randomized controlled trials (RCTs) of omega-3 PUFA treatment of depressive disorders, taking into account the clinical differences among patients included in the studies.MethodsA search on MEDLINE, EMBASE, PsycInfo, and the Cochrane Database of RCTs using omega-3 PUFA on patients with depressive symptoms published up to August 2013 was performed. Standardized mean difference in clinical measure of depression severity was primary outcome. Type of omega-3 used (particularly eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and omega-3 as mono- or adjuvant therapy was also examined. Meta-regression analyses assessed the effects of study size, baseline depression severity, trial duration, dose of omega-3, and age of patients.ResultsMeta-analysis of 11 and 8 trials conducted respectively on patients with a DSM-defined diagnosis of major depressive disorder (MDD) and patients with depressive symptomatology but no diagnosis of MDD demonstrated significant clinical benefit of omega-3 PUFA treatment compared to placebo (standardized difference in random-effects model 0.56 SD [95% CI: 0.20, 0.92] and 0.22 SD [95% CI: 0.01, 0.43], respectively; pooled analysis was 0.38 SD [95% CI: 0.18, 0.59]). Use of mainly EPA within the preparation, rather than DHA, influenced final clinical efficacy. Significant clinical efficacy had the use of omega-3 PUFA as adjuvant rather than mono-therapy. No relation between efficacy and study size, baseline depression severity, trial duration, age of patients, and study quality was found. Omega-3 PUFA resulted effective in RCTs on patients with bipolar disorder, whereas no evidence was found for those exploring their efficacy on depressive symptoms in young populations, perinatal depression, primary disease other than depression and healthy subjects.ConclusionsThe use of omega-3 PUFA is effective in patients with diagnosis of MDD and on depressive patients without diagnosis of MDD.

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“…Expression of the ILEI transcript in human brain has been described 22 . However, the function of ILEI in the nervous system remains largely unknown, except for its possible role in development of the Xenopus retina 38 is associated with an increased risk of AD 40 , and the neuronal expression of TGF-b type II receptors is reduced in AD brains from the early stage of disease development 31 . In addition, recent proteomic analysis of cerebrospinal fluid revealed significantly decreased ILEI levels in patients with idiopathic temporal lobe epilepsy 41 , in whom the age-related incidence of Ab plaques in temporal cortex is significantly higher compared with agematched controls 42 .…”

Section: Discussionmentioning

confidence: 99%

The FAM3 superfamily member ILEI ameliorates Alzheimer’s disease-like pathology by destabilizing the penultimate amyloid-β precursor

et al. 2014

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Accumulation of amyloid-b peptide (Ab) in the brain underlies the pathogenesis of Alzheimer's disease (AD). Ab is produced by b-and g-secretase-mediated sequential proteolysis of amyloid-b precursor protein (APP). Here we identify a secretory protein named interleukinlike epithelial-mesenchymal transition inducer (ILEI, also known as FAM3 superfamily member C) as a negative regulator of Ab production. ILEI destabilizes the b-secretasecleaved APP carboxy-terminal fragment, the penultimate precursor of Ab, by binding to the g-secretase complex and interfering with its chaperone properties. Notch signalling and g-secretase activity are not affected by ILEI. We also show neuronal expression of ILEI and its induction by transforming growth factor-b signalling. The level of secreted ILEI is markedly decreased in the brains of AD patients. Transgenic (Tg) overexpression of ILEI significantly reduces the brain Ab burden and ameliorates the memory deficit in AD model mice. ILEI may be a plausible target for the development of disease-modifying therapies.

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The CC genotype of transforming growth factor-β1 increases the risk of late-onset Alzheimer's disease and is associated with AD-related depression

Cited by 49 publications

References 74 publications

Inflammatory Cytokines and Alzheimer’s Disease: A Review from the Perspective of Genetic Polymorphisms

Inflammatory Cytokines and Alzheimer’s Disease: A Review from the Perspective of Genetic Polymorphisms

Role of Omega-3 Fatty Acids in the Treatment of Depressive Disorders: A Comprehensive Meta-Analysis of Randomized Clinical Trials

The FAM3 superfamily member ILEI ameliorates Alzheimer’s disease-like pathology by destabilizing the penultimate amyloid-β precursor

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