Patricia Manzine
Federal University of São Carlos
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Publication
Featured researches published by Patricia Manzine.
Dementia and Geriatric Cognitive Disorders | 2013
Patricia Manzine; Jessyka Maria de França Bram; Elisabeth Joan Barham; Francisco Assis Carvalho Vale; Heloisa S. Selistre-de-Araujo; Márcia Regina Cominetti; Sofia Cristina Iost Pavarini
Alzheimer’s disease (AD) is the most common cause of dementia in people above age 65. Platelet studies with ADAM10 have shown that its expression is reduced in AD patients. The aim of this research was to compare the platelet levels of ADAM10 protein in two Brazilian elderly groups, considering the stages of the disease. The SDS-PAGE technique followed by Western blotting was used. Data were analyzed using comparison, correlation and association statistical methods. The results showed reduced platelet ADAM10 levels in AD elderly compared to non-AD subjects. The disease progression intensified this reduction. ADAM10 was the only statistically significant variable (p = 0.01) to increase the AD occurrence probability. The cutoff value of 0.4212 in the receiver operating characteristic curve captured sensitivity and specificity of 70 and 80.77%, respectively. Together with other clinical criteria, ADAM10 seems to be a relevant biomarker tool for early and accurate AD diagnosis.
Biomarkers | 2015
Patricia Manzine; Elena Marcello; Barbara Borroni; Willem Kamphuis; Elly M. Hol; Alessandro Padovani; Carla Manuela Crispim Nascimento; Patricia De Godoy Bueno; Francisco Assis Carvalho Vale; Sofia Cristina Iost Pavarini; Monica Di Luca; Márcia Regina Cominetti
Abstract ADAM10 is a potential biomarker for Alzheimers disease (AD). ADAM10 protein levels are reduced in platelets of AD patients. The aim was to verify the total blood and platelet ADAM10 gene expression in AD patients and to compare with mild cognitive impairment (MCI) and healthy subjects. No significant differences in ADAM10 gene expression were observed. Therefore, the decrease of ADAM10 protein in platelets of AD patients is not caused by a reduction in ADAM10 mRNA. Further studies must be performed to investigate other pathways in the down regulation of ADAM10 protein.
International Journal of Geriatric Psychiatry | 2014
Patricia Manzine; Elizabeth Joan Barham; Francisco Assis Carvalho Vale; Heloisa S. Selistre-de-Araujo; Sofia Cristina Iost Pavarini; Márcia Regina Cominetti
Earlier studies have demonstrated that a disintegrin and metallopeptidase 10 (ADAM10) levels are reduced in Alzheimers disease (AD) patients compared with healthy subjects. The objective of this study was to evaluate whether platelet ADAM10 levels correlates with the clock drawing test (CDT) scores, which is a simple and a reliable measure of visuospatial ability and executive function in AD patients.
Journal of Alzheimer's Disease | 2013
Patricia Manzine; Elisabeth Joan Barham; Francisco Assis Carvalho Vale; Heloisa S. Selistre-de-Araujo; Sofia Cristina Iost Pavarini; Márcia Regina Cominetti
BACKGROUND Previous studies have demonstrated a decrease in platelet ADAM10 expression among patients with Alzheimers disease (AD) and healthy matched subjects. The association between cognitive tests and molecular biomarkers, such as platelet ADAM10, may contribute to an accurate AD diagnosis. OBJECTIVE The aim of this research was to investigate whether cognitive deficits in AD, assessed by Mini-Mental State Exam (MMSE), correlate with ADAM10 platelet levels and if that contributes to a more effective AD diagnosis. METHODS Elderly patients with probable AD (n = 30) and a non-AD control group (n = 25), matched by age, gender, and education level were evaluated. Platelet proteins were analyzed on SDS-PAGE (10%) and ADAM10 expression was identified by western blotting. β-actin was used as the endogenous control. The Spearman correlation coefficient between ADAM10 and MMSE ratio was obtained for each group. RESULTS The MMSE ratio of AD subjects (0.45 ± 0.32) was significantly different (p < 0.001) compared to the non-AD group (1.14 ± 0.07). The relationship between MMSE ratio and ADAM10 expression was significant (r = 0.62, p = 0.0003) for the AD group. The combination of ADAM10 and MMSE at a cutoff ≤ 0.87 presented a sensitivity of 85%, and a specificity of 97% (AUC 0.99, 95% CI 0.92 -1.00), which was significantly better for AD diagnosis than the AUCs of MMSE (p = 0.05) and ADAM10 expression (p = 0.18) separately. CONCLUSIONS The association of MMSE and ADAM10 expression was significantly better compared with MMSE and ADAM10 expression separately, thus providing and additional diagnostic tool for AD.
Journal of Alzheimer's Disease | 2017
Patricia Manzine; Silvia Pelucchi; Maria Aderuza Horst; Francisco Assis Carvalho Vale; Sofia Cristina Iost Pavarini; Matteo Audano; Nico Mitro; Monica Di Luca; Elena Marcello; Márcia Regina Cominetti
ADAM10 is the α-secretase that cleaves amyloid-β protein precursor in the non-amyloidogenic pathway in Alzheimers disease (AD) and is known to be regulated by different microRNAs (miRNAs), which are post-transcriptional regulators related to several biological and pathological processes, including AD. Here we proposed to explore and validate miRNAs that have direct or indirect relations to the AD pathophysiology and ADAM10 gene. Approximately 700 miRNAs were analyzed and 21 differentially expressed miRNAs were validated in a sample of 21 AD subjects and 17 cognitively healthy matched controls. SH-SY5Y cells were transfected with miR-144-5p, miR-221, and miR-374 mimics and inhibitors, and ADAM10 protein levels were evaluated. miR-144-5p, miR-221, and miR-374 were downregulated in AD. The overexpression of miR-221 in SH-SY5Y cells resulted in ADAM10 reduction and its inhibition in ADAM10 increased. These findings show that miR-221 can be a new potential therapeutic target for increasing ADAM10 levels in AD. In addition, these results can contribute to the better understanding of ADAM10 post-transcriptional regulation.
Dementia & Neuropsychologia | 2009
Patricia Manzine; Sofia Cristina Iost Pavarini
The aim of this study was to review the scientific publications on cognitive rehabilitation in Alzheimer’s disease by year published and methodology employed. The principles of systematic review by the Brazilian Cochrane Center were used. Reviews conducted by this Center were identified together with those held on the LILACS and Medline scientific databases. Nine levels of evidence were considered for analysis and a total of 37 articles were found. The results showed a growing number of publications from 2001 onwards, with majority being published early this decade. Few studies have been published on cognitive rehabilitation, with an average of three articles published per year during the study period (1985–2008). The highest levels of evidence were observed in the more recently published studies. Cognitive rehabilitation can yield greater benefits in rehabilitating patients when associated with other forms of intervention. The latest studies demonstrating greater scientific evidence concluded that results remain limited and that further studies on the topic are needed.
International Psychogeriatrics | 2016
Otávio Augusto Fernandes Marques Bianco; Patricia Manzine; Carla Manuela Crispim Nascimento; Francisco Assis Carvalho Vale; Sofia Cristina Iost Pavarini; Márcia Regina Cominetti
BACKGROUND Studies have demonstrated a decreased platelet ADAM10 expression in patients with Alzheimers Disease (AD), classifying this protein as a blood-based AD biomarker. About 50% of the patients with AD are diagnosed with depression, which is commonly treated with tricyclic and tetracyclic antidepressants, monoaminoxidade (MAO) inhibitors and, more preferably, with selective serotonin reuptake inhibitors (SSRIs). Considering that a large proportion of patients with AD takes antidepressant medications during the course of the disease we investigated the influence of this medication on the expression of platelet ADAM10, which is considered the main α-secretase preventing beta-amyloid (βA) formation. METHODS Blood was collected for protein extraction from platelets. ADAM10 was analyzed by using western blotting and reactive bands were measured using β-actin as endogenous control. RESULTS Platelet ADAM10 protein expression in patients with AD was positively influenced by serotoninergic medication. CONCLUSION More studies on the positive effects of serotonergic antidepressants on ADAM10 platelet expression should be performed in order to understand its biological mechanisms and to verify whether these effects are reflected in the central nervous system. This work represents an important advance for the study of AD biomarkers, as well as for more effective pharmacological treatment of patients with AD and associated depression.
Pharmaceuticals | 2018
Rafaela Peron; Izabela Vatanabe; Patricia Manzine; Antoni Camins; Márcia Regina Cominetti
ADAM (a disintegrin and metalloproteinase) is a family of widely expressed, transmembrane and secreted proteins of approximately 750 amino acids in length with functions in cell adhesion and proteolytic processing of the ectodomains of diverse cell-surface receptors and signaling molecules. ADAM10 is the main α-secretase that cleaves APP (amyloid precursor protein) in the non-amyloidogenic pathway inhibiting the formation of β-amyloid peptide, whose accumulation and aggregation leads to neuronal degeneration in Alzheimer’s disease (AD). ADAM10 is a membrane-anchored metalloprotease that sheds, besides APP, the ectodomain of a large variety of cell-surface proteins including cytokines, adhesion molecules and notch. APP cleavage by ADAM10 results in the production of an APP-derived fragment, sAPPα, which is neuroprotective. As increased ADAM10 activity protects the brain from β-amyloid deposition in AD, this strategy has been proved to be effective in treating neurodegenerative diseases, including AD. Here, we describe the physiological mechanisms regulating ADAM10 expression at different levels, aiming to propose strategies for AD treatment. We report in this review on the physiological regulation of ADAM10 at the transcriptional level, by epigenetic factors, miRNAs and/or translational and post-translational levels. In addition, we describe the conditions that can change ADAM10 expression in vitro and in vivo, and discuss how this knowledge may help in AD treatment. Regulation of ADAM10 is achieved by multiple mechanisms that include transcriptional, translational and post-translational strategies, which we will summarize in this review.
Pharmaceuticals | 2018
Jaume Folch; Miren Ettcheto; Oriol Busquets; Elena Sánchez-López; Rubén Darío Castro-Torres; Ester Verdaguer; Patricia Manzine; Saghar Poor; María Ángeles García; Jordi Olloquequi; Carlos Beas-Zarate; Carme Auladell; Antoni Camins
Alzheimer’s disease (AD) is progressive neurodegenerative disorder characterized by brain accumulation of the amyloid β peptide (Aβ), which form senile plaques, neurofibrillary tangles (NFT) and, eventually, neurodegeneration and cognitive impairment. Interestingly, epidemiological studies have described a relationship between type 2 diabetes mellitus (T2DM) and this pathology, being one of the risk factors for the development of AD pathogenesis. Information as it is, it would point out that, impairment in insulin signalling and glucose metabolism, in central as well as peripheral systems, would be one of the reasons for the cognitive decline. Brain insulin resistance, also known as Type 3 diabetes, leads to the increase of Aβ production and TAU phosphorylation, mitochondrial dysfunction, oxidative stress, protein misfolding, and cognitive impairment, which are all hallmarks of AD. Moreover, given the complexity of interlocking mechanisms found in late onset AD (LOAD) pathogenesis, more data is being obtained. Recent evidence showed that Aβ42 generated in the brain would impact negatively on the hypothalamus, accelerating the “peripheral” symptomatology of AD. In this situation, Aβ42 production would induce hypothalamic dysfunction that would favour peripheral hyperglycaemia due to down regulation of the liver insulin receptor. The objective of this review is to discuss the existing evidence supporting the concept that brain insulin resistance and altered glucose metabolism play an important role in pathogenesis of LOAD. Furthermore, we discuss AD treatment approaches targeting insulin signalling using anti-diabetic drugs and mTOR inhibitors.
Alzheimers & Dementia | 2017
Patricia Manzine; Silvia Pelucchi; Elena Marcello; Maria Aderuza Horst; Francisco Assis Carvalho Vale; Sofia Cristina Iost Pavarini; Monica DiLuca; Márcia Regina Cominetti
Representative image of western blot analysis of the endogenous ADAM10 protein in SH-SY5Y cells transfected with the negative control or miR-1445p: miR-221, miR-374 mimics. Actin served as an internal control. (B) Quantitative analysis of experiments in (A). Optical densities of ADAM10 bands from five independent experiments were quantified and normalized to the corresponding actin bands. The values were plotted as fold-change with respect to the negative control (miR-144-5p 79.83 6 26.76%; miR-221 57.65 6 14.64%; miR-374 86.80 6 21.31%; * miR221 vs negative control P1⁄40.04). Poster Presentations: Monday, July 17, 2017 P673