Vanessa Gomes Fraga

Resolution of inflammation, n − 3 fatty acid supplementation and Alzheimer disease: A narrative review

In patients with Alzheimers disease (AD), a persistent and unresolved neuroinflammatory process can contribute to neuronal loss and a decline in their cognitive and functional abilities. Recent studies have demonstrated that the ability to resolve inflammation is impaired in the brains of patients with AD. Preclinical evidence demonstrates the potential of therapeutic interventions on the resolution phase of inflammation in AD. Supplementation of omega-3 fatty acids (n-3 FAs), precursors for specialized pro-resolving mediators, emerged as a possibility for prevention and management of AD. Here, we provide a narrative review of resolving inflammation in AD and the role of n-3 FA supplementation in AD.

Genetic predisposition to higher production of interleukin-6 through -174 G > C polymorphism predicts global cognitive decline in oldest-old with cognitive impairment no dementia.

Interleukin 6 (IL-6) is a pro-inflammatory cytokine upregulated in neurodegenerative contexts. The polymorphism IL-6 -174 G > C influences release levels of this cytokine. We aimed to evaluate the influence of IL-6 -174 G > C on global cognitive score of a group with cognitive impairment no dementia in one year of follow-up.Methods The subjects were categorized in two groups: short-term decline in global cognitive score and those with short-term stability or improvement. IL-6 174 G > C information were compared among these groups.Results We observed that individuals with cognitive impairment no dementia with GGlowergenotype were more frequent among global cognitive score non-decliners while carriers of at least one Chigherallele were more frequent in the group with global cognitive score decliners (p = 0.012; RR = 3.095 IC95%= 1.087-8.812).Conclusion These results suggest that the higher expression of IL-6 gene may be an independent risk factor for cognitive decline among individuals with cognitive impairment no dementia.

TGF-β1 Codon 10 T>C Polymorphism Influences Short-Term Functional and Cognitive Decline in Healthy Oldest-Old Individuals: The Pietà Study

BACKGROUND Inflammation and cytokine production are a common finding in aging, which probably exert influence on cognitive and functional abilities in elderly people. Transforming-growth-factor beta 1 (TGF-β1) is an important multifunctional anti-inflammatory cytokine that displays immunomodulatory activities. OBJECTIVE This prospective investigation aimed to evaluate the TGF-β1 codon 10 T>C on functional and cognitive decline in subjects aged 75+ years. METHODS The Functional Activities Questionnaire evaluated the functional performance and the cognitive assessment was evaluated through brief cognitive tests, consisting of: the Mini-Mental State Examination, animal category fluency test, and picture drawings memory test. All tests were administered twice, with a one-year interval. RESULTS Carriers of Tlower allele showed significant short-term decline in cognitive and functional performance, while individuals with CChigher genotype of TGF-β1 codon 10 T>C remained stable or showed improvement. CONCLUSION Our findings indicate that the lower production of TGF-β1 could predict a longitudinal functional and cognitive decline in oldest-old individuals.

Polymorphisms in cytokine genes influence cognitive and functional performance in a population aged 75 years and above: Cytokine SNPs influences cognition and functionality in elderlies

To investigate the frequency of the cytokine single nucleotide polymorphisms (SNPs) tumor necrosis factor (TNF)‐α −308G > A, tumor growth factor (TGF)‐β1 codon +10C > T, TGF‐β1 codon +25G > C, interleukin (IL)‐10 −1082A > G, IL‐10 −819C > T, IL‐10 −592C > A, IL‐6 −174G > C, and IFN‐γ +874T > A in a sample of healthy and cognitively impaired elderlies and to verify the probable association between these SNPs and cognitive and functional performance of subjects aged 75 years and above.

EVALUATION OF PLATELET P-SELECTIN IN PATIENTS WITH ALZHEIMER'S DISEASE AND FRONTOTEMPORAL DEMENTIA

Background: Alcadeina (Alca) is a member of alcadein family composed of Alca, Alcb and Alcg, which is largely expressed in brain neuron and prone to form a tripartite complex with APP mediated by cytoplasmic neural-specific adaptor protein X11like (X11L). p3-Alca is generated from Alca by cleavage of aand g-secretases, and secreted into cerebrospinal fluid (CSF) and then into blood as does Ab from APP. The p3-Alca35 exists in CSF as a major species, as like as Ab40, while p3-Alca38 is minor as like as Ab42. p3-Alca is non-aggregatable so easily detected in CSF and plasma by sELISA (Hata 2009). To establish an effective AD diagnosis, we verified p3-Alca38/35, a ratio of p3-Alca38 to p3-Alca35. Methods: Previously, we showed the plasma level of p3-Alca35 using sELISAwith p3-Alca35 specific antibody (Omori 2014). To measure p3-Alca38/35 level, we tried to prepare new antibody raised to p3-Alca38 with higher affinity. Using cell surface display method, p3-Alca38 chimeric protein was expressed on cell surface and the cells were immunized. Several clones generating antibody specifically react to p3Alca38 were isolated, and we developed new sELISA system to quantify p3-Alca38 with higher sensitivity. Results:We first characterized the new sELISA systems to quantify p3-Alca38. With a combination of sELISA to quantify p3-Alca35, both p3-Alca35 and p3-Alca38 in body fluid were quantified. The levels p3Alca38/35 ratio in MCI and AD subjects showed a tendency increasing along with cognitive impairment degree compared to non-demented controls. The p3-Alca38/35 ratio significantly increased along with the increase of Ab42/40 ratio in vitro, while in vivo, the significant increase of p3-Alca38/35 correlated with the significant decrease of Ab42/40. Conclusions:Our study suggested that p3-Alca38/35 can be an effective biomarker of AD not only in CSF but also in plasma, which indicates a qualitative change of g-secretase activity. Further studies with samples from various cohorts (for example, with chronologically chasing and taking samples) will be performed to confirm the efficiency of p3-Alca38/35 as a biomarker to find prodromal and/or early stage MCI/AD subjects who shows an altered/attenuated g-secretase activity.

Blood neuron cell-derived microparticles as potential biomarkers in Alzheimer’s disease

Carolina A. Magalhães, Fernanda M. Campos, Cristina M.G. Loures, Vanessa G. Fraga, Ana Carolina R. Oliveira, Amanda C. Chaves, Natália P. Rocha, Leonardo C. de Souza, Raphael D. Maia, Henrique C. Guimarães, Marco Túlio G. Cintra, Elvis C.C. Mateo, Maria Aparecida C. Bicalho, Maria das Graças Carvalho, Lirlândia P. Sousa, Paulo Caramelli and Karina B. Gomes* Blood neuron cell-derived microparticles as potential biomarkers in Alzheimer’s disease

Troponin as a cardiotoxicity marker in breast cancer patients receiving anthracycline-based chemotherapy: A narrative review

The approach to breast cancer has changed in recent decades due to significant advances in screening, early diagnosis, and treatment; however, the risk of cardiovascular injury induced by chemotherapy has remained similar. Anthracyclines are the most common agents used in breast cancer treatment and may lead to cardiotoxicity, which appears to have a direct relationship with accumulated dose and duration of treatment. Therefore, the use of cardiac biomarkers derived from those used in cardiac disease diagnosis has been applied to the early identification, evaluation, and cardiotoxicity monitoring during chemotherapy. Cardiac troponins (cTn) have high specificities and high sensitivity in myocardial injury and are used in the diagnosis and risk stratification of acute coronary syndromes. cTn have been validated by clinical studies in the cardiotoxicity diagnosis and prognosis in patients treated with high doses of anthracyclines alone or in combination, mainly with trastuzumab. Thus, the identification of cardiotoxicity through cTn in the preclinical phase would be crucial for the application of preventive strategies. Here, we analyzed 23 cross-sectional, prospective and retrospective studies using cTn as the biomarker of cardiotoxicity in patients with breast cancer receiving treatment with anthracyclines. Studies showed that the association of cTn with different biomarkers can contribute to the early diagnosis of cardiotoxicity; however the main evidence is that low cTn levels is related to a better outcome with a good negative predictive value (NPV). In conclusion, different studies are still necessary for the adoption of cTn as a routine clinical biomarker in patients with breast cancer receiving anthracycline treatment.

MICROPARTICLES DERIVED FROM TISSUE FACTOR, LEUKOCYTE, ENDOTHELIUM AND NEURON ARE ASSOCIATED WITH ALZHEIMER’S DISEASE

panel of rat (APPsi) and mouse (Tg4-42) biofluids and tissues. This give further help to understand the devastating neurodegenerative disease, related complex biochemical pathways and pathophysiological processes of AD.Conclusions:UsingNMR-basedmetabolic phenotyping we defined a quantitative readout of transgenic animal models in the form of a biomarker panel. These biomarkers not only contribute to the understanding of this devastating neurodegenerative disease and the related pathophysiological processes on a systemic level, but set the base for a wide range of biomedical applications. Our approach can be easily extended to other tissues, matrices, or disease models and translated across species since metabolic pathways are conserved through evolution, and are essentially similar in rodents and humans.

Adiponectin gene polymorphisms: Association with childhood obesity

The current childhood obesity epidemic represents a particular challenge for public health. Understanding of the etiological mechanisms of obesity remains integral in treating this complex disorder. In recent years, studies have elucidated the influence of hormones secreted by adipose tissue named adipokines. Adiponectin is a adipokine that exhibits important anti-inflammatory, insulin-sensitizing and anti-atherogenic properties and it is strongly associated to obesity development. It is well known that adiponectin levels decrease with obesity. Furthermore, studies show that some single nucleotide polymorphisms in the gene encoding adiponectin, ADIPOQ, may influence the expression of this protein. The objective of this paper is to provide an up-to-date review of ADIPOQ polymorphisms in the context of childhood obesity.

Cerebrospinal fluid biomarkers for the differential diagnosis of Alzheimer’s disease

Introduction: Several studies have been conducted in order to validate cerebrospinal fluid biomarkers for the diagnosis of Alzheimer’s disease (AD), aiming primarily to facilitate the early diagnosis. Objective: To evaluate CSF biomarkers on patients with probable AD and the applicability of the international references values in this population. Methods: 46 individuals were recruited and classified as probable AD (n = 19), mild cognitive impairment (MCI) (n = 5) and other dementias (n = 22). The cerebrospinal fluid (CSF) biomarkers were measured using the INNOTEST kits for enzyme-linked immunosorbent assay (ELISA). Higher Tau protein values and lower Aβand Innotest Amyloid Tau Index (IATI) values were observed in AD group when compared with MCI; higher levels of Tau and phosphorylated Tau (P-Tau), and lower Aβand IATI values were observed in AD group when compared to patients with other dementias. No biomarker or IATI was able to distinguish between MCI and other dementias. The kappa index between biomarkers and the clinical diagnosis was regular to Tau and IATI, and weak to Aβand P-tau. Conclusion: The cut-off values for each biomarker that showed better combined sensibility and specificity differ from the reference values suggested by the manufacturer. The CSF biomarkers represent important resources that can help with the AD diagnosis, although the results interpretation must be made based on the analysis of the three analytes together. The cut-off values must be established to address the specificities and characteristics of each population.