RENATA ELAINE PARAIZO LEITE
Projetos de Pesquisa
Unidades Organizacionais
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
- Chronic Traumatic Encephalopathy Presenting as Alzheimer's Disease in a Retired Soccer Player(2016) GRINBERG, Lea T.; ANGHINAH, Renato; NASCIMENTO, Camila Fernandes; AMARO JR., Edson; LEITE, Renata P.; MARTIN, Maria da Graca M.; NASLAVSKY, Michel S.; TAKADA, Leonel T.; JACOB FILHO, Wilson; PASQUALUCCI, Carlos A.; NITRINI, RicardoThe relationship between soccer and chronic traumatic encephalopathy (CTE) is not well established. We report clinicopathological correlations in an 83-year-old retired center-back soccer player, with no history of concussion, manifesting typical Alzheimer-type dementia. Examination revealed mixed pathology including widespread CTE, moderate Alzheimer's disease, hippocampal sclerosis, and TDP-43 proteinopathy. This case adds to a few CTE cases described in soccer players. Furthermore, it corroborates that CTE may present clinically as typical Alzheimer-type dementia. Further studies investigating the extent to which soccer is a risk for CTE are needed.
- Do age and sex impact on the absolute cell numbers of human brain regions?(2016) OLIVEIRA-PINTO, Ana V.; ANDRADE-MORAES, Carlos H.; OLIVEIRA, Lays M.; PARENTE-BRUNO, Danielle R.; SANTOS, Raquel M.; COUTINHO, Renan A.; ALHO, Ana T. L.; LEITE, Renata E. P.; SUEMOTO, Claudia K.; GRINBERG, Lea T.; PASQUALUCCI, Carlos A.; JACOB-FILHO, Wilson; LENT, RobertoWhat is the influence of sex and age on the quantitative cell composition of the human brain? By using the isotropic fractionator to estimate absolute cell numbers in selected brain regions, we looked for sex- and age-related differences in 32 medial temporal lobes (comprised basically by the hippocampal formation, amygdala and parahippocampal gyrus), sixteen male (29-92 years) and sixteen female (25-82); and 31 cerebella, seventeen male (29-92 years) and fourteen female (25-82). These regions were dissected from the brain, fixed and homogenized, and then labeled with a DNA-marker (to count all nuclei) and with a neuron-specific nuclear marker (to estimate neuron number). Total number of cells in the medial temporal lobe was found to be 1.91 billion in men, and 1.47 billion in women, a difference of 23 %. This region showed 34 % more neurons in men than in women: 525.1 million against 347.4 million. In contrast, no sex differences were found in the cerebellum. Regarding the influence of age, a quadratic correlation was found between neuronal numbers and age in the female medial temporal lobe, suggesting an early increase followed by slight decline after age 50. The cerebellum showed numerical stability along aging for both neurons and non-neuronal cells. In sum, results indicate a sex-related regional difference in total and neuronal cell numbers in the medial temporal lobe, but not in the cerebellum. On the other hand, aging was found to impact on cell numbers in the medial temporal lobe, while the cerebellum proved resilient to neuronal losses in the course of life.
- d Argyrophilic Grain Disease: Demographics, Clinical, and Neuropathological Features From a Large Autopsy Study(2016) RODRIGUEZ, Roberta Diehl; SUEMOTO, Claudia Kimie; MOLINA, Mariana; NASCIMENTO, Camila Fernandes; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; FARFEL, Jose Marcelo; HEINSEN, Helmut; NITRINI, Ricardo; UEDA, Kenji; PASQUALUCCI, Carlos Augusto; JACOB-FILHO, Wilson; YAFFE, Kristine; GRINBERG, Lea TenenholzArgyrophilic grain disease (AGD) is a frequent late-onset, 4 repeat tauopathy reported in Caucasians with high educational attainment. Little is known about AGD in non-Caucasians or in those with low educational attainment. We describe AGD demographics, clinical, and neuropathological features in a multiethnic cohort of 983 subjects >50 years of age from Sao Paulo, Brazil. Clinical data were collected through semistructured interviews with an informant and included in the Informant Questionnaire on Cognitive Decline in the Elderly, the Clinical Dementia Rating, and the Neuropsychiatric Inventory. Neuropathologic assessment relied on internationally accepted criteria. AGD was frequent (15.2%) and was the only neuropathological diagnosis in 8.9% of all cases (mean, 78.9 +/- 9.4 years); it rarely occurred as an isolated neuropathological finding. AGD was associated with older age, lower socioeconomic status (SES), and appetite disorders. This is the first study of demographic, clinical, and neuropathological aspects of AGD in different ethnicities and subjects from all socioeconomic strata. The results suggest that prospective studies of AGD patients include levels of hormones related to appetite control as possible antemortem markers. Moreover, understanding the mechanisms behind higher susceptibility to AGD of low SES subjects may disclose novel environmental risk factors for AGD and other neurodegenerative diseases.
- Association between adiposity and systemic atherosclerosis: a protocol of a cross-sectional autopsy study(2016) NISHIZAWA, Aline; SUEMOTO, Claudia Kimie; FARIAS, Daniela Souza; CAMPOS, Fernanda Marinho; SILVA, Karen Cristina Souza da; CUELHO, Anderson; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; GRINBERG, Lea Tenenholz; FARFEL, Jose Marcelo; JACOB-FILHO, Wilson; PASQUALUCCI, Carlos AugustoIntroduction: Adiposity has been associated with atherosclerosis in clinical studies. However, few autopsy studies have investigated this association, and they had only examined the coronary artery disease. Moreover, most studies had small sample sizes and were limited to middle-aged or young adults. Our aim is to investigate the association between adiposity and systemic atherosclerosis in an autopsy study. Methods and analysis: A sample of 240 deceased with 30 years or more will be evaluated. The sample size was calculated using the lowest correlation coefficient found in previous studies (r=0.109), assuming a power of 90% and alpha=0.05. We will collect information about sociodemographics, frequency of previous contact of the deceased's next of kin and cardiovascular risk factors. We will measure neck, waist and hip circumferences, weight, height and abdominal subcutaneous tissue thickness, and then we will calculate the body mass index, waist-to-hip ratio, waist-to-height ratio and body shape index. We will also weigh the pericardial and abdominal visceral fat, the heart, and we will measure the left ventricular wall thickness. We will evaluate the presence of myocardial infarction, the degree of atherosclerosis in the aorta, carotid, coronary and cerebral arteries and plaque composition in carotid, coronary and cerebral arteries. For each individual, we will fix arterial and adipose tissue samples in 10% formalin and freeze another adipose tissue sample at -80 degrees C for future studies. Ethics and dissemination: Ethical approval was granted by the Ethics Committee of University of Sao Paulo Medical School, Brazil. Results will be submitted for publication in a peer-reviewed journal.
- Three-dimensional and stereological characterization of the human substantia nigra during aging(2016) ALHO, Ana Tereza Di Lorenzo; SUEMOTO, Claudia Kimie; POLICHISO, Livia; TAMPELLINI, Edilaine; OLIVEIRA, Katia Cristina de; MOLINA, Mariana; SANTOS, Glaucia Aparecida Bento; NASCIMENTO, Camila; LEITE, Renata Elaine Paraizo; FERRETI-REBUSTINI, Renata Eloah de Lucena; SILVA, Alexandre Valotta da; NITRINI, Ricardo; PASQUALUCCI, Carlos Augusto; JACOB-FILHO, Wilson; HEINSEN, Helmut; GRINBERG, Lea TenenholzThe human brain undergoes non-uniform changes during aging. The substantia nigra (SN), the source of major dopaminergic pathways in the brain, is particularly vulnerable to changes in the progression of several age-related neurodegenerative diseases. To establish normative data for high-resolution imaging, and to further clinical and anatomical studies we analyzed SNs from 15 subjects aged 50-91 cognitively normal human subjects without signs of parkinsonism. Complete brains or brainstems with substantia nigra were formalin-fixed, celloidin-mounted, serially cut and Nissl-stained. The shapes of all SNs investigated were reconstructed using fast, high-resolution computer-assisted 3D reconstruction software. We found a negative correlation between age and SN volume (p = 0.04, rho = -0.53), with great variability in neuronal numbers and density across participants. The 3D reconstructions revealed SN inter- and intra-individual variability. Furthermore, we observed that human SN is a neuronal reticulum, rather than a group of isolated neuronal islands. Caution is required when using SN volume as a surrogate for SN status in individual subjects. The use of multimodal sequences including those for fiber tracts may enhance the value of imaging as a diagnostic tool to assess SN in vivo. Further studies with a larger sample size are needed for understanding the structure-function interaction of human SN.
- Perivascular Adipose Tissue Inflammation and Coronary Artery Disease: An Autopsy Study Protocol(2016) FARIAS-ITAO, Daniela Souza; PASQUALUCCI, Carlos Augusto; NISHIZAWA, Aline; SILVA, Luiz Fernando Ferraz; CAMPOS, Fernanda Marinho; SILVA, Karen Cristina Souza da; LEITE, Renata Elaine Paraizo; GRINBERG, Lea Tenenholz; FERRETTI-REBUSTINI, Renata Eloah Lucena; JACOB FILHO, Wilson; SUEMOTO, Claudia KimieBackground: Perivascular adipose tissue (PAT) inflammation may have a role in coronary artery disease (CAD) pathophysiology. However, most evidence has come from samples obtained during surgical procedures that may imply in some limitations. Moreover, the role of B lymphocytes and inflammation in PAT that is adjacent to unstable atheroma plaques has not been investigated in humans using morphometric measurements. Objective: The objective of this study is to investigate the inflammation in PAT, subcutaneous, and perirenal adipose tissues (SAT and PrAT) among chronic CAD, acute CAD, and control groups in an autopsy study. Methods: Heart, SAT, and PrAT samples are collected from autopsied subjects in a general autopsy service, with the written informed consent of the next-of-kin (NOK). Sociodemographic and clinical data are obtained from a semistructure interview with the NOK. Coronary arteries are dissected and PAT are removed. Sections with the greatest arterial obstruction or unstable plaques, and the local with absence of atherosclerosis in all coronary arteries are sampled. PAT are represented adjacent to these fragments. Adipose tissues are fixed in 4% buffered paraformaldehyde solution and analyzed immunohistochemically for macrophages (CD68), macrophage polarization (CD11c for proinflammatory and CD206 for anti-inflammatory), B lymphocytes (CD20), and T lymphocytes (CD3). Slides will be scanned, and inflammatory cells will be quantified in 20 random fields. Participants will be categorized in CAD groups, after morphometric measurement of arterial obstruction and plaque composition analysis in accordance with American Heart Association classification. Three study groups will be investigated: acute CAD (at least one unstable plaque); chronic CAD (>= 50% arterial obstruction); and controls (< 50% arterial obstruction). Inflammatory cells in PAT, SAT, and PrAT will be counted and compared between groups using multivariate linear regression, adjusted for age, body mass index, hypertension, diabetes, alcohol use, and smoking. Results: We present the methods of our study that was developed from 2 pilots. Currently, data collection and tissue processing are ongoing. Data collection, histology and immunochemistry procedures, and quantification of all inflammatory cells are expected to be concluded within 1 year. Conclusions: This study will contribute for the understanding of the mechanisms of CAD pathophysiology because it will help to clarify the role of inflammation both in chronic and acute CAD.
- Acetylated tau destabilizes the cytoskeleton in the axon initial segment and is mislocalized to the somatodendritic compartment(2016) SOHN, Peter Dongmin; TRACY, Tara E.; SON, Hye-In; ZHOU, Yungui; LEITE, Renata E. P.; MILLER, Bruce L.; SEELEY, William W.; GRINBERG, Lea T.; GAN, LiBackground: Neurons are highly polarized cells in which asymmetric axonal-dendritic distribution of proteins is crucial for neuronal function. Loss of polarized distribution of the axonal protein tau is an early sign of Alzheimer's disease (AD) and other neurodegenerative disorders. The cytoskeletal network in the axon initial segment (AIS) forms a barrier between the axon and the somatodentritic compartment, contributing to axonal retention of tau. Although perturbation of the AIS cytoskeleton has been implicated in neurological disorders, the molecular triggers and functional consequence of AIS perturbation are incompletely understood. Results: Here we report that tau acetylation and consequent destabilization of the AIS cytoskeleton promote the somatodendritic mislocalization of tau. AIS cytoskeletal proteins, including ankyrin G and beta IV-spectrin, were downregulated in AD brains and negatively correlated with an increase in tau acetylated at K274 and K281. AIS proteins were also diminished in transgenic mice expressing tauK274/281Q, a tau mutant that mimics K274 and K281 acetylation. In primary neuronal cultures, the tauK274/281Q mutant caused hyperdynamic microtubules (MTs) in the AIS, shown by live-imaging of MT mobility and fluorescence recovery after photobleaching. Using photoconvertible tau constructs, we found that axonal tauK274/281Q was missorted into the somatodendritic compartment. Stabilizing MTs with epothilone D to restore the cytoskeletal barrier in the AIS prevented tau mislocalization in primary neuronal cultures. Conclusions: Together, these findings demonstrate that tau acetylation contributes to the pathogenesis of neurodegenerative disease by compromising the cytoskeletal sorting machinery in the AIS.
- Higher Prevalence of TDP-43 Proteinopathy in Cognitively Normal Asians: A Clinicopathological Study on a Multiethnic Sample(2016) NASCIMENTO, Camila; SUEMOTO, Claudia K.; RODRIGUEZ, Roberta D.; ALHO, Ana Tereza Di Lorenzo; LEITE, Renata P.; FARFEL, Jose Marcelo; PASQUALUCCI, Carlos Augusto Goncalves; JACOB-FILHO, Wilson; GRINBERG, Lea T.Transactive response DNA binding protein 43 (TDP-43) proteinopathy is the major hallmark of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. It is also present in a subset of Alzheimer's disease cases. Recently, few reports showed TDP-43 changes in cognitively normal elderly. In Caucasians, TDP-43 proteinopathy independently correlate with cognitive decline. However, it is challenging to establish direct links between cognitive and/or neuropsychiatric symptoms and protein inclusions in neurodegenerative diseases because individual cognitive reserves modify the threshold for clinical disease expression. Cognitive reserve is influenced by demographic, environmental and genetic factors. We investigated the relationships between demographic, clinical and neuropathological variables and TDP-43 proteinopathy in a large multiethnic sample of cognitively normal elderly. TDP-43 proteinopathy was identified in 10.5%, independently associated with older age (P=0.03) and Asian ethnicity (P=0.002). Asians showed a higher prevalence of TDP-43 proteinopathy than Caucasians, even after adjustment for sex, age, Braak stage and schooling (odds ratio=3.50, confidence interval 1.41-8.69, P=0.007). These findings suggested that Asian older adults may be protected from the clinical manifestation of brain TDP-43 proteinopathy. Future studies are needed to identify possible race-related protective factors against clinical expression of TDP-43 proteinopathies.