RENATA ELAINE PARAIZO LEITE

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LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina

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Autor e Coautores FMUSP-HC Normalizados: CAMILA NASCIMENTO MANTELLI ×

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  • article 27 Citação(ões) na Scopus
    Prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults: systematic review and meta-analysis
    (2018) NASCIMENTO, C.; ALHO, A. T. Di Lorenzo; AMARAL, C. Bazan Conceicao; LEITE, R. E. P.; NITRINI, R.; JACOB-FILHO, W.; PASQUALUCCI, C. A.; HOKKANEN, S. R. K.; HUNTER, S.; KEAGE, H.; KOVACS, G. G.; GRINBERG, L. T.; SUEMOTO, C. K.
    ObjectiveTo perform a systematic review and meta-analysis on the prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults. MethodsWe systematically reviewed and performed a meta-analysis on the prevalence of TDP-43 proteinopathy in older adults with normal cognition, evaluated by the Mini-Mental State Examination or the Clinical Dementia Rating. We estimated the overall prevalence of TDP-43 using random-effect models, and stratified by age, sex, sample size, study quality, antibody used to assess TDP-43 aggregates, analysed brain regions, Braak stage, Consortium to Establish a Registry for Alzheimer's Disease score, hippocampal sclerosis and geographic location. ResultsA total of 505 articles were identified in the systematic review, and 7 were included in the meta-analysis with 1196 cognitively normal older adults. We found an overall prevalence of TDP-43 proteinopathy of 24%. Prevalence of TDP-43 proteinopathy varied widely across geographic location (North America: 37%, Asia: 29%, Europe: 14%, and Latin America: 11%). Estimated prevalence of TDP-43 proteinopathy also varied according to study quality (quality score >7: 22% vs. quality score <7: 42%), antibody used to assess TDP-43 proteinopathy (native: 18% vs. hyperphosphorylated: 24%) and presence of hippocampal sclerosis (without 24% vs. with hippocampal sclerosis: 48%). Other stratified analyses by age, sex, analysed brain regions, sample size and severity of AD neuropathology showed similar pooled TDP-43 prevalence. ConclusionsDifferent methodology to access TDP-43, and also differences in lifestyle and genetic factors across different populations could explain our results. Standardization of TDP-43 measurement, and future studies about the impact of genetic and lifestyle characteristics on the development of neurodegenerative diseases are needed.
  • article 46 Citação(ões) na Scopus
    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, Ricardo
    The 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.
  • conferenceObject
    Inflammatory factors (cytokines and cortisol) across different brain regions in bipolar disorder and their associations with neuropsychiatric symptoms: A post-mortem study
    (2020) NASCIMENTO, Camila; NUNES, Paula V.; SUEMOTO, Claudia K.; RODRIGUEZ, Roberta D.; LEITE, Renata E. P.; GRINBERG, Lea T.; PASQUALUCCI, Carlos A.; NITRINI, Ricardo; JACOB-FILHO, Wilson; BRENTANI, Helena P.; LAFER, Beny
  • article 128 Citação(ões) na Scopus
    Quantifying the accretion of hyperphosphorylated tau in the locus coeruleus and dorsal raphe nucleus: the pathological building blocks of early Alzheimer's disease
    (2017) EHRENBERG, A. J.; NGUY, A. K.; THEOFILAS, P.; DUNLOP, S.; SUEMOTO, C. K.; ALHO, A. T. Di Lorenzo; LEITE, R. P.; RODRIGUEZ, R. Diehl; MEJIA, M. B.; RUEB, U.; FARFEL, J. M.; FERRETTI-REBUSTINI, R. E. de Lucena; NASCIMENTO, C. F.; NITRINI, R.; PASQUALLUCCI, C. A.; JACOB-FILHO, W.; MILLER, B.; SEELEY, W. W.; HEINSEN, H.; GRINBERG, L. T.
    AimsHyperphosphorylated tau neuronal cytoplasmic inclusions (ht-NCI) are the best protein correlate of clinical decline in Alzheimer's disease (AD). Qualitative evidence identifies ht-NCI accumulating in the isodendritic core before the entorhinal cortex. Here, we used unbiased stereology to quantify ht-NCI burden in the locus coeruleus (LC) and dorsal raphe nucleus (DRN), aiming to characterize the impact of AD pathology in these nuclei with a focus on early stages.MethodsWe utilized unbiased stereology in a sample of 48 well-characterized subjects enriched for controls and early AD stages. ht-NCI counts were estimated in 60-m-thick sections immunostained for p-tau throughout LC and DRN. Data were integrated with unbiased estimates of LC and DRN neuronal population for a subset of cases.ResultsIn Braak stage 0, 7.9% and 2.6% of neurons in LC and DRN, respectively, harbour ht-NCIs. Although the number of ht-NCI+ neurons significantly increased by about 1.9x between Braak stages 0 to I in LC (P = 0.02), we failed to detect any significant difference between Braak stage I and II. Also, the number of ht-NCI+ neurons remained stable in DRN between all stages 0 and II. Finally, the differential susceptibility to tau inclusions among nuclear subdivisions was more notable in LC than in DRN.ConclusionsLC and DRN neurons exhibited ht-NCI during AD precortical stages. The ht-NCI increases along AD progression on both nuclei, but quantitative changes in LC precede DRN changes.
  • conferenceObject
    Brain transcriptome analysis of Japanese population living in Brazil
    (2019) MARIE, Suely Kazue Nagahashi; LERARIO, Antonio Marcondes; SHINJO, Sueli Mieko Oba; NASCIMENTO, Camila; LEITE, Renata; SUEMOTO, Claudia; PASQUALUCCI, Carlos Augusto; MURAYAMA, Shigeo
  • conferenceObject
    Unrevealing the role of a frontotemporal dementia protein (TDP-43 protein) in bipolar disorder
    (2019) NASCIMENTO, C.; VILLELA, P. Nunes; KIM, H. Kyunghee; OLIVEIRA, K. De; LEITE, R. E. Paraizo; FERRETTI-REBUSTINI, R. E. D. L.; GRINBERG, L. T.; SUEMOTO, C. K.; PASQUALUCCI, C. A.; NITRINI, R.; JACOB-FILHO, W.; BRENTANI, H. P.; LAFER, B.
  • article 231 Citação(ões) na Scopus
    Locus coeruleus volume and cell population changes during Alzheimer's disease progression: A stereological study in human postmortem brains with potential implication for early-stage biomarker discovery
    (2017) THEOFILAS, Panos; EHRENBERG, Alexander J.; DUNLOP, Sara; ALHO, Ana T. Di Lorenzo; NGUY, Austin; LEITE, Renata Elaine Paraizo; RODRIGUEZ, Roberta Diehl; MEJIA, Maria B.; SUEMOTO, Claudia K.; FERRETTI-REBUSTINI, Renata Eloah De Lucena; POLICHISO, Livia; NASCIMENTO, Camila F.; SEELEY, William W.; NITRINI, Ricardo; PASQUALUCCI, Carlos Augusto; JACOB FILHO, Wilson; RUEB, Udo; NEUHAUS, John; HEINSEN, Helmut; GRINBERG, Lea T.
    Introduction: Alzheimer's disease (AD) progression follows a specific spreading pattern, emphasizing the need to characterize those brain areas that degenerate first. The brainstem's locus coeruleus (LC) is the first area to develop neurofibrillary changes (neurofibrillary tangles [NFTs]). Methods: The methods include unbiased stereologiCal analyses in human brainstems to estimate LC volume and neuronal population in controls and individuals across all AD stages. Results: As the Braak stage increases by 1 unit, the LC volume decreases by 8.4%. Neuronal loss started only midway through AD progression. Age-related changes spare the LC. Discussion: The long gap between NFT accumulation and neuronal loss suggests that a second trigger may be necessary to induce neuronal death in AD. Imaging studies should determine whether LC volumetry can replicate the stage-wise atrophy observed here and how these changes are specific to AD. LC volumetry may develop into a screening biomarker for selecting high-yield candidates to undergo expensive and less accessible positron emission tomography scans and to monitor AD progression from presymptomatic stages.
  • article 8 Citação(ões) na Scopus
    Factors associated with brain volume in major depression in older adults without dementia: results from a large autopsy study
    (2018) NUNES, Paula Villela; SUEMOTO, Claudia Kimie; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; PASQUALUCCI, Carlos Augusto; NITRINI, Ricardo; FARFEL, Jose Marcelo; OLIVEIRA, Katia Cristina de; GRINBERG, Lea Tenenholz; COSTA, Nicole Rezende da; NASCIMENTO, Camila Fernandes; SALMASI, Faraz; KIM, Helena Kyunghee; YOUNG, Lionel Trevor; JACOB-FILHO, Wilson; LAFER, Beny
    ObjectiveWe examined brain volume and atrophy in individuals with major depressive disorder (MDD) without dementia that were referred to a large autopsy service. We also examined potential risk factors for brain atrophy, including demographics and clinical variables. MethodsIn this study, 1373 participants (787 male) aged 50years or older who died from natural causes were included. Participants with no reliable informant, with cognitive impairment or dementia, with a medical history of severe chronic disease, or with prolonged agonal state were excluded. Presence of MDD at least once in their lifetime was defined according to the Structured Clinical Interview for DSM. Brain volume was measured immediately after removal from the skull. ResultsMean age at death was 68.611.6, and MDD was present in 185 (14%) individuals. Smaller brain volume was associated with older age (p<0.001), lower education (years; p<0.001), hypertension (p=0.001), diabetes (p=0.006), and female gender (p<0.001). In the multivariate analysis adjusted for sociodemographics and cardiovascular risk factors, smaller brain volume was not associated with major depression (=-0.86, 95% CI=-26.50 to 24.77, p=0.95). ConclusionsIn this large autopsy study of older adults, MDD was not associated with smaller brain volumes. Regardless of the presence of MDD, in this sample of older adults without dementia, we found that smaller brain volumes were associated with risk factors for brain neurodegeneration such as older age, diabetes, hypertension, and lower education.
  • article 58 Citação(ões) na Scopus
    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 Tenenholz
    Argyrophilic 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.
  • conferenceObject
    Determinants of microcephaly in adults using data mining: increased risk for dementia and greater association with male gender
    (2020) MANCINE, L.; SUEMOTO, C. K.; RODRIGUEZ, R. D.; LEITE, R. E. P.; NASCIMENTO, C.; FERRETI-REBUSTINI, R.; TEIXEIRA, J. D. M.; PASQUALUCCI, C. A.; NITRINI, R.; JACOB-FILHO, W.; GRINBERG, L.; SALVINI, R.; NUNES, P. V.