JOSE MARCELO FARFEL
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Ortopediae Traumatologia, Faculdade de Medicina - Docente
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina
18 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 18
- 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.
- Sex differences in Alzheimer's disease and common neuropathologies of aging(2018) OVEISGHARAN, Shahram; ARVANITAKIS, Zoe; YU, Lei; FARFEL, Jose; SCHNEIDER, Julie A.; BENNETT, David A.Alzheimer's dementia is significantly more common in women than in men. However, few pathological studies have addressed sex difference in Alzheimer's disease (AD) and other brain pathologies. We leveraged postmortem data from 1453 persons who participated in one of two longitudinal community-based studies of older adults, the Religious Orders Study and the Rush Memory and Aging Project. Postmortem examination identified AD pathologies, neocortical Lewy bodies, DNA-binding protein 43 (TDP-43), hippocampal sclerosis, gross and micro infarcts, atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy. Linear and logistic regressions examined the association of sex with each of the pathologic measures. Two-thirds of subjects were women (n=971; 67%), with a mean age at death of 89.8 (SD=6.6) years in women and 87.3 (SD=6.6) in men. Adjusted for age and education, women had higher levels on a global measure of AD pathology (estimate=0.102, SE=0.022, p<0.001), and tau tangle density in particular (estimate=0.334, SE=0.074, p<0.001), and there was a borderline difference between women and men in amyloid- load (estimate=0.124, SE=0.065, p=0.056). In addition, compared to men, women were more likely to have more severe arteriolosclerosis (OR=1.28, 95% CI:1.04-1.58, p=0.018), and less likely to have gross infarcts (OR=0.78, 95% CI:0.61-0.98, p=0.037), although the association with gross infarct was attenuated after controlling for vascular risk factors. These data help elucidate the neuropathologic footprint of sex difference in AD and other common brain pathologies of aging.
- Atherosclerosis and Dementia A Cross-Sectional Study With Pathological Analysis of the Carotid Arteries(2011) SUEMOTO, Claudia K.; NITRINI, Ricardo; GRINBERG, Lea T.; FERRETTI, Renata E. L.; FARFEL, Jose M.; LEITE, Renata E. P.; MENEZES, Paulo R.; FREGNI, Felipe; JACOB-FILHO, Wilson; PASQUALUCCI, Carlos A.Background and Purpose-Previous ultrasound-based studies have shown an association between carotid artery atherosclerosis and dementia. Our aim was to investigate this association using postmortem examination. Methods-Postmortem morphometric measurements of carotid stenosis and intima-media thickness were performed in individuals with dementia (n = 112) and control subjects (n = 577). Multivariate logistic regression models were applied. Results-High-grade left internal carotid stenosis (>= 70%) was associated with increased odds for dementia (OR, 2.30; 95% CI, 1.14-4.74; P = 0.02). Intima-media thickness was not associated with dementia. Conclusions-The likelihood of dementia is increased with high-grade left internal carotid artery atherosclerosis after adjusting for demographic and cardiovascular risk factors. (Stroke. 2011; 42: 3614-3615.)
conferenceObject TRANSCRIPTOME STUDY IN STRIATUM OF OBSESSIVE COMPULSIVE DISORDERS (POSTMORTEM STUDY)(2017) LISBOA, Bianca; OLIVEIRA, Katia de; LIMA, Luzia Carreira; PUGA, Renato; RIBEIRO, Gustavo; TAHIRA, Ana; FARFEL, Jose Marcelo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; JACOB-FILHO, Wilson; MIGUEL, Euripedes Constantino; PAULS, David; SHAVITT, Roseli; HOEXTER, Marcelo; PEREIRA, Carlos Alberto de Braganca; BRENTANI, Helena- 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.
- Very low levels of education and cognitive reserve A clinicopathologic study(2013) FARFEL, Jose Marcelo; NITRINI, Ricardo; SUEMOTO, Claudia Kimie; GRINBERG, Lea Tenenholz; FERRETTI, Renata Eloah Lucena; LEITE, Renata Elaine Paraizo; TAMPELLINI, Edilaine; LIMA, Luzia; FARIAS, Daniela Souza; NEVES, Ricardo Caires; RODRIGUEZ, Roberta Diehl; MENEZES, Paulo Rossi; FREGNI, Felipe; BENNETT, David A.; PASQUALUCCI, Carlos Augusto; JACOB FILHO, WilsonObjective: We conducted a clinicopathologic study in a large population with very low levels of education to determine whether very few years of education could contribute to cognitive reserve and modify the relation of neuropathologic indices to dementia. Methods: In this cross-sectional study, we included 675 individuals 50 years of age or older from the Brazilian Aging Brain Study Group. Cognitive abilities were evaluated through a structured interview with an informant at the time of autopsy, including the Clinical Dementia Rating (CDR) scale. Neuropathologic examinations were performed using immunohistochemistry and following internationally accepted criteria. Multivariate linear regression models were conducted to determine whether the association between cognitive abilities (measured by CDR sum of boxes) and years of education was independent of sociodemographic variables and neuropathologic indices, including neuritic plaques, neurofibrillary tangles, lacunar infarctions, small-vessel disease, and Lewy bodies. In addition, interaction models were used to examine whether education modified the relation between neuropathologic indices and cognition. Results: Mean education was 3.9 +/- 3.5 years. Formal education was associated with a lower CDR sum of boxes (beta = -0.197; 95% confidence interval -0.343, -0.052; p = 0.008), after adjustment for sociodemographic variables and neuropathologic indices. Furthermore, education modified the relationship of lacunar infarcts with cognitive abilities (p = 0.04). Conclusions: Even a few years of formal education contributes to cognitive reserve.
conferenceObject Transactive response DNA-binding protein 43 as a neuromarker of bipolar disorder(2018) NASCIMENTO, C.; VILLELA, P. Nunes; OLIVEIRA, K. C. De; BARBOSA, A.; KIM, H. Kyunghee; MORETTO, A. C.; LEITE, R. E. Paraizo; FERRETTI-REBUSTINI, R. Eloah de Lucena; GRINBERG, L. Tenenholz; SUEMOTO, C. Kimie; FARFEL, J. M.; PASQUALUCCI, C. A.; BRENTANI, H. P.; NITRINI, R.; JACOB-FILHO, W.; LAFER, B.article 48 Citação(ões) na Scopus Relation of genomic variants for Alzheimer disease dementia to common neuropathologies(2016) FARFEL, Jose M.; YU, Lei; BUCHMAN, Aron S.; SCHNEIDER, Julie A.; JAGER, Philip L. De; BENNETT, David A.Objective: To investigate the associations of previously reported Alzheimer disease (AD) dementia genomic variants with common neuropathologies. Methods: This is a postmortem study including 1,017 autopsied participants from 2 clinicopathologic cohorts. Analyses focused on 22 genomic variants associated with AD dementia in largescale case-control genome-wide association study (GWAS) meta-analyses. The neuropathologic traits of interest were a pathologic diagnosis of AD according to NIA-Reagan criteria, macroscopic and microscopic infarcts, Lewy bodies (LB), and hippocampal sclerosis. For each variant, multiple logistic regression was used to investigate its association with neuropathologic traits, adjusting for age, sex, and subpopulation structure. We also conducted power analyses to estimate the sample sizes required to detect genome-wide significance (p < 5 X 10(-8)) for pathologic AD for all variants. Results: APOE epsilon 4 allele was associated with greater odds of pathologic AD (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.67-5.46, p = 1.9 X 10(-13)), while epsilon 2 allele was associated with lower odds of pathologic AD (OR 0.42, 95% CI 0.30-0.61, p = 3.1 X 10(-6)). Four additional genomic variants including rs6656401 (CR1), rs1476679 (ZCWPW1), rs35349669 (INPP5D), and rs17125944 (FERMT2) had p values less than 0.05. Remarkably, half of the previously reported AD dementia variants are not likely to be detected for association with pathologic AD with a sample size in excess of the largest GWAS meta-analyses of AD dementia. Conclusions: Many recently discovered genomic variants for AD dementia are not associated with the pathology of AD. Some genomic variants for AD dementia appear to be associated with other common neuropathologies.- Diabetes mellitus, alzheimer disease and vascular dementia: a clinicopathologic study(2015) MATIOLI, M. N. P. S.; SUEMOTO, C. K.; FARFEL, J. M.; FARIAS, D. S.; NEVES, R. C.; LEITE, R. E. P.; PASQUALUCCI, C. A.; JACOB FILHO, W.; GRINBERG, L. T.; NITRINI, R.
conferenceObject Increased levels of TDP-43 protein in postmortem brain tissue of bipolar disorder subjects(2017) NASCIMENTO, C.; KIM, H. Kyunghee; OLIVEIRA, K. Cristina de; MORETTO, A. C.; BRENTANI, H. P.; ANDREAZZA, A.; LEITE, R. E. Paraizo; FERRETTI-REBUSTINI, R. E. D. L.; SUEMOTO, C. Kimie; PASQUALUCCI, C. Augusto; NITRINI, R.; FARFEL, J. M.; JACOB-FILHO, W.; NUNES, P. Villela; LAFER, B.