CARLOS AUGUSTO GONCALVES PASQUALUCCI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
ATCIENT-50, SVOC
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina - Líder
ATCIENT-50, SVOC
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina - Líder
128 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 128
- 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.
- Low brain-derived neurotrophic factor levels in post-mortem brains of older adults with depression and dementia in a large clinicopathological sample(2018) NUNES, Paula Villela; NASCIMENTO, Camila Fernandes; KIM, Helena Kyunghee; ANDREAZZA, Ana Cristina; BRENTANI, Helena Paula; SUEMOTO, Claudia Kimie; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; PASQUALUCCI, Carlos Augusto; NITRINI, Ricardo; GRINBERG, Lea Tenenholz; YONG, Lionel Trevor; JACOB-FILHO, Wilson; LAFER, BenyBackground: Disturbances in peripheral brain-derived neurotrophic factor (BDNF) have been reported in major depressive disorder (MDD). However, there are no studies measuring BDNF levels directly in post-mortem brains of older subjects with MDD and dementia. We aimed to verify if brain BDNF levels were lower in older adults with lifetime history of MDD with and without dementia. Methods: BDNF levels of post-mortem brains from 80 community-dwelling older individuals with lifetime MDD with and without dementia were compared with levels from 80 controls without lifetime MDD. Participants with no reliable close informant, or with prolonged agonal state were excluded. Lifetime MDD was defined as at least one previous episode according to the Structured Clinical Interview for DSM (SCID). Results: BDNF levels were lower in the MDD group with dementia than in participants with dementia and without MDD as confirmed by multivariate analysis adjusted for clinical and cardiovascular risk factors (beta = - 0.106, 95%CI = - 0.204; - 0.009, p = 0.034). No difference was found in the group with MDD without dementia compared with their controls. Limitations: The retrospective assessment of a lifetime history of depression may be subject to information bias and this study only establishes a cross-sectional association between lifetime history of MDD and lower levels of BDNF in patients with dementia. Conclusions: In this community sample of older individuals, lower brain BDNF levels were found in cases with both lifetime MDD and dementia. Low BDNF levels could be a moderator to accelerated brain aging observed in MDD with dementia.
- Determination of antidepressants in whole blood using hollow-fiber liquid-phase microextraction and gas chromatography-mass spectrometry(2014) SANTOS, Marcelo Filonzi dos; FERRI, Caio Caleiras; SEULIN, Saskia Carolina; LEYTON, Vilma; PASQUALUCCI, Carlos Augusto Goncalves; MUNOZ, Daniel Romero; YONAMINE, MauricioA hollow-fiber liquid-phase microextraction (HF-LPME), used in three-phase mode, and combined with gas chromatography-mass spectrometry (GC-MS), was developed to quantify antidepressants and their major metabolites (amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, desmethylclomipramine, fluoxetine, and norfluoxetine) in whole blood samples, using their deuterated analogs as internal standards. The HF-LPME system comprised a disposable 8-cm polypropylene porous hollow fiber, 4.0 ml of sample solution (0.5 ml of blood added to 3.5 ml of 0.1 M NaOH: donor phase), dodecane (organic phase), and 0.1 M formic acid (acceptor phase) for extraction. After stirring the system, the acceptor phase was evaporated under a nitrogen stream and resuspended in 30 mu l of methanol. Derivatization was not required. A 2.0-mu l aliquot of this solution was injected into a GC-MS system. The method was validated after the optimization of several parameters that may influence the extraction efficiency. The limits of quantification for all antidepressants were below the therapeutic levels (20.0 ng/ml). The average intraday and interday precisions were within 9.7 and 9.8 %, respectively, for all analytes. The calibration curves were linear in the concentration range of 20-1,200 ng/ml. The developed method was applied to seven actual postmortem samples. Tricyclic antidepressants were detected in all of the analyzed cases. To our knowledge, this is the first demonstration of usefulness of HF-LPME for analysis of antidepressants in postmortem forensic cases.
- 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.
- Magnetic resonance diffusion tensor imaging for the pedunculopontine nucleus: proof of concept and histological correlation(2017) ALHO, A. T. D. L.; HAMANI, C.; ALHO, E. J. L.; SILVA, R. E. da; SANTOS, G. A. B.; NEVES, R. C.; CARREIRA, L. L.; ARAUJO, C. M. M.; MAGALHAES, G.; COELHO, D. B.; ALEGRO, M. C.; MARTIN, M. G. M.; GRINBERG, L. T.; PASQUALUCCI, C. A.; HEINSEN, H.; FONOFF, E. T.; AMARO JR., E.The pedunculopontine nucleus (PPN) has been proposed as target for deep brain stimulation (DBS) in patients with postural instability and gait disorders due to its involvement in muscle tonus adjustments and control of locomotion. However, it is a deep-seated brainstem nucleus without clear imaging or electrophysiological markers. Some studies suggested that diffusion tensor imaging (DTI) may help guiding electrode placement in the PPN by showing the surrounding fiber bundles, but none have provided a direct histological correlation. We investigated DTI fractional anisotropy (FA) maps from in vivo and in situ postmortem magnetic resonance images (MRI) compared to histological evaluations for improving PPN targeting in humans. A post-mortem brain was scanned in a clinical 3T MR system in situ. Thereafter, the brain was processed with a special method ideally suited for cytoarchitectonic analyses. Also, nine volunteers had in vivo brain scanning using the same MRI protocol. Images from volunteers were compared to those obtained in the post-mortem study. FA values of the volunteers were obtained from PPN, inferior colliculus, cerebellar crossing fibers and medial lemniscus using histological data and atlas information. FA values in the PPN were significantly lower than in the surrounding white matter region and higher than in areas with predominantly gray matter. In Nissl-stained histologic sections, the PPN extended for more than 10 mm in the rostro-caudal axis being closely attached to the lateral parabrachial nucleus. Our DTI analyses and the spatial correlation with histological findings proposed a location for PPN that matched the position assigned to this nucleus in the literature. Coregistration of neuroimaging and cytoarchitectonic features can add value to help establishing functional architectonics of the PPN and facilitate neurosurgical targeting of this extended nucleus.
- Education, but not occupation, is associated with cognitive impairment: The role of cognitive reserve in a sample from a low-to-middle-income country(2022) SUEMOTO, Claudia K.; BERTOLA, Laiss; GRINBERG, Lea T.; LEITE, Renata E. P.; RODRIGUEZ, Roberta D.; SANTANA, Pedro H.; PASQUALUCCI, Carlos A.; JACOB-FILHO, Wilson; NITRINI, RicardoIntroduction Education, and less frequently occupation, has been associated with lower dementia risk in studies from high-income countries. We aimed to investigate the association of cognitive impairment with education and occupation in a low-middle-income country sample. Methods In this cross-sectional study, cognitive function was assessed by the Clinical Dementia Rating sum of boxes (CDR-SOB). We investigated the association of occupation complexity and education with CDR-SOB using adjusted linear regression models for age, sex, and neuropathological lesions. Results In 1023 participants, 77% had < 5 years of education, and 56% unskilled occupations. Compared to the group without education, those with formal education had lower CDR-SOB (1-4 years: beta= -0.99, 95% confidence interval [CI] = -1.85; -0.14, P = .02; >= 5 years: beta= -1.42, 95% CI = -2.47; -0.38, P = .008). Occupation complexity and demands were unrelated to cognition. Discussion Education, but not occupation, was related to better cognitive abilities independent of the presence of neuropathological insults.
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- The influence of age and sex on the absolute cell numbers of the human brain cerebral cortex(2023) CASTRO-FONSECA, Emily; MORAIS, Viviane; SILVA, Camila G. da; WOLLNER, Juliana; FREITAS, Jaqueline; MELLO-NETO, Arthur F.; OLIVEIRA, Luiz E.; OLIVEIRA, Vilson C. de; LEITE, Renata E. P.; ALHO, Ana T.; RODRIGUEZ, Roberta D.; FERRETTI-REBUSTINI, Renata E. L.; SUEMOTO, Claudia K.; JACOB-FILHO, Wilson; NITRINI, Ricardo; PASQUALUCCI, Carlos A.; GRINBERG, Lea T.; TOVAR-MOLL, Fernanda; LENT, RobertoThe human cerebral cortex is one of the most evolved regions of the brain, responsible for most higher-order neural functions. Since nerve cells (together with synapses) are the processing units underlying cortical physiology and morphology, we studied how the human neocortex is composed regarding the number of cells as a function of sex and age. We used the isotropic fractionator for cell quantification of immunocytochemically labeled nuclei from the cerebral cortex donated by 43 cognitively healthy subjects aged 25-87 years old. In addition to previously reported sexual dimorphism in the medial temporal lobe, we found more neurons in the occipital lobe of men, higher neuronal density in women's frontal lobe, but no sex differences in the number and density of cells in the other lobes and the whole neocortex. On average, the neocortex has similar to 10.2 billion neurons, 34% in the frontal lobe and the remaining 66% uniformly distributed among the other 3 lobes. Along typical aging, there is a loss of non-neuronal cells in the frontal lobe and the preservation of the number of neurons in the cortex. Our study made possible to determine the different degrees of modulation that sex and age evoke on cortical cellularity.
- Transcriptomic analysis of purified human cortical microglia reveals age-associated changes(2017) GALATRO, Thais F.; HOLTMAN, Inge R.; LERARIO, Antonio M.; VAINCHTEIN, Ilia D.; BROUWER, Nieske; SOLA, Paula R.; VERAS, Mariana M.; PEREIRA, Tulio F.; LEITE, Renata E. P.; MOLLER, Thomas; WES, Paul D.; SOGAYAR, Mari C.; LAMAN, Jon D.; DUNNEN, Wilfred den; PASQUALUCCI, Carlos A.; OBA-SHINJO, Sueli M.; BODDEKE, Erik W. G. M.; MARIE, Suely K. N.; EGGEN, Bart J. L.Microglia are essential for CNS homeostasis and innate neuroimmune function, and play important roles in neurodegeneration and brain aging. Here we present gene expression profiles of purified microglia isolated at autopsy from the parietal cortex of 39 human subjects with intact cognition. Overall, genes expressed by human microglia were similar to those in mouse, including established microglial genes CX3CR1, P2RY12 and ITGAM (CD11B). However, a number of immune genes, not identified as part of the mouse microglial signature, were abundantly expressed in human microglia, including TLR, F-c gamma and SIGLEC receptors, as well as TAL1 and IFI16, regulators of proliferation and cell cycle. Age-associated changes in human microglia were enriched for genes involved in cell adhesion, axonal guidance, cell surface receptor expression and actin (dis)assembly. Limited overlap was observed in microglial genes regulated during aging between mice and humans, indicating that human and mouse microglia age differently.
- 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.