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
7 resultados
Resultados de Busca
Agora exibindo 1 - 7 de 7
- 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 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, HelenaconferenceObject 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.- Neuropathological diagnoses and clinical correlates in older adults in Brazil: A cross-sectional study(2017) SUEMOTO, Claudia K.; FERRETTI-REBUSTINI, Renata E. L.; RODRIGUEZ, Roberta D.; LEITE, Renata E. P.; SOTERIO, Luciana; BRUCKI, Sonia M. D.; SPERA, Raphael R.; CIPPICIANI, Tarcila M.; FARFEL, Jose M.; CHIAVEGATTO FILHO, Alexandre; NASLAYSKY, Michel Satya; ZATZ, Mayana; PASQUALUCCI, Carlos A.; JACOB-FILHO, Wilson; NITRINI, Ricardo; GRINBERG, Lea T.Background Clinicopathological studies are important in determining the brain lesions underlying dementia. Although almost 60% of individuals with dementia live in developing countries, few clinicopathological studies focus on these individuals. We investigated the frequency of neurodegenerative and vascular-related neuropathological lesions in 1,092 Brazilian admixed older adults, their correlation with cognitive and neuropsychiatric symptoms, and the accuracy of dementia subtype diagnosis. Methods and findings In this cross-sectional study, we describe clinical and neuropathological variables related to cognitive impairment in 1,092 participants (mean age = 74 y, 49% male, 69% white, and mean education = 4 y). Cognitive function was investigated using the Clinical Dementia Rating (CDR) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE); neuropsychiatric symptoms were evaluated using the Neuropsychiatric Inventory (NPI). Associations between neuropathological lesions and cognitive impairment were investigated using ordinal logistic regression. We developed a neuropathological comorbidity (NPC) score and compared it to CDR, IQCODE, and NPI scores. We also described and compared the frequency of neuropathological diagnosis to clinical diagnosis of dementia subtype. Forty-four percent of the sample met criteria for neuropathological diagnosis. Among these participants, 50% had neuropathological diagnoses of Alzheimer disease (AD), and 35% of vascular dementia (VaD). Neurofibrillary tangles (NFTs), hippocampal sclerosis, lacunar infarcts, hyaline atherosclerosis, siderocalcinosis, and Lewy body disease were independently associated with cognitive impairment. Higher NPC scores were associated with worse scores in the CDR sum of boxes (beta = 1.33, 95% CI 1.20-1.46), IQCODE (beta = 0.14, 95% CI 0.13-0.16), and NPI (beta = 1.74, 95% CI = 1.33-2.16). Compared to neuropathological diagnoses, clinical diagnosis had high sensitivity to AD and high specificity to dementia with Lewy body/Parkinson dementia. The major limitation of our study is the lack of clinical follow-up of participants during life. Conclusions NFT deposition, vascular lesions, and high NPC scorewere associated with cognitive impairment in a unique Brazilian sample with low education. Our results confirm the high prevalence of neuropathological diagnosis in older adults and the mismatch between clinical and neuropathological diagnoses.
- Diabetes is Not Associated with Alzheimer's Disease Neuropathology(2017) MATIOLI, Maria Niures Pimentel dos Santos; SUEMOTO, Claudia Kimie; RODRIGUEZ, Roberta Diehl; FARIAS, Daniela Souza; SILVA, Magnolia Moreira da; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah Lucena; FARFEL, Jose Marcelo; PASQUALUCCI, Carlos Augusto; JACOB FILHO, Wilson; ARVANITAKIS, Zoe; NASLAYSKY, Michel Satya; ZATZ, Mayana; GRINBERG, Lea Tenenholz; NITRINI, RicardoBackground: Previous evidence linking diabetes to Alzheimer's disease (AD) neuropathology is mixed and scant data are available from low-and middle-income countries. Objective: To investigate the association between diabetes and AD neuropathology in a large autopsy study of older Brazilian adults. Methods: In this cross-sectional study, diabetes was defined by diagnosis during life or use of antidiabetic medication. A standardized neuropathological examination was performed using immunohistochemistry. The associations of diabetes with Consortium to Establish and Registry for Alzheimer Disease (CERAD) scores for neuritic plaques and Braak-Braak (BB) scores for neurofibrillary tangles were investigated using multivariable ordinal logistic regression. We investigated effect modification of education, race, and APOE on these associations. Results: Among 1,037 subjects (mean age = 74.4 +/- 11.5 y; mean education = 4.0 +/- 3.7 y; 48% male, 61% White), diabetes was present in 279 subjects. Diabetes was not associated with BB (OR = 1.12, 95% CI = 0.81-1.54, p = 0.48) or with CERAD (OR = 0.97, 95% CI = 0.68-1.38, p = 0.86) scores on analyses adjusted for sociodemographic and clinical variables. We observed effect modification by the APOE allele epsilon 4 on the association between diabetes mellitus and BB scores. Conclusion: No evidence of an association between diabetes and AD neuropathology was found in a large sample of Brazilians; however, certain subgroups, such as APOE allele epsilon 4 carriers, had higher odds of accumulation of neurofibrillary tangles.
- Morphometric measurements of systemic atherosclerosis and visceral fat: Evidence from an autopsy study(2017) NISHIZAWA, Aline; SUEMOTO, Claudia K.; FARIAS-ITAO, Daniela S.; CAMPOS, Fernanda M.; SILVA, Karen C. S.; BITTENCOURT, Marcio S.; GRINBERG, Lea T.; LEITE, Renata E. P.; FERRETTI-REBUSTINI, Renata E. L.; FARFEL, Jose M.; JACOB-FILHO, Wilson; PASQUALUCCI, Carlos A.Background Morphometric measurements of systemic atherosclerosis and direct quantification of visceral fat are only possible using materials from autopsy studies. However, the few autopsy studies that have investigated the association of visceral fat with atherosclerosis had small sample sizes and focused on coronary arteries of young or middle-aged White subjects. We aimed to investigate the association of pericardial fat (PF) and abdominal visceral fat (AVF) with atherosclerosis in the aorta, coronary, carotid, and cerebral arteries in a large autopsy study. Materials and methods We evaluated deceased subjects aged 30 years or above. We dissected and weighted the PF and the AVF and evaluated the atherosclerotic burden in the aorta, as well as the carotid, coronary, and cerebral arteries using morphometric measurements. We also investigated the interaction of PF and AVF with age regarding the atherosclerotic burden. Results The mean age of the 240 included subjects was 64.8 +/- 15.3 years, and 63% was male. Greater PF was associated with a higher degree of aortic atherosclerosis after adjusting for confounding variables (coefficient = 4.39, 95% CI = 0.83; 7.94, p = 0.02). Greater AVF was associated with a higher coronary stenosis index (coefficient = 1.49, 95% CI = 0.15; 2.83, p = 0.03) and a greater number of coronary plaques (coefficient = 0.71, 95% CI = 0.24; 1.19, p = 0.003). We did not find an association of PF or AVF with carotid or cerebral atherosclerotic burden. We found a significant interaction of AVF (coefficient = -0.08; 95% CI = -0.14; -0.02, p = 0.009) and PF (coefficient = -0.87, 95% CI = -1.70; -0.04, p = 0.04) with age regarding carotid artery atherosclerotic burden. Conclusions Greater AVF was associated with greater atherosclerotic burden and extent in coronary arteries, while greater PF correlated with a higher degree of atherosclerosis in the aorta.
- Neuropathologic features of TOMM40 ' 523 variant on late-life cognitive decline(2017) YU, Lei; LUTZ, Michael W.; FARFEL, Jose M.; WILSON, Robert S.; BURNS, Daniel K.; SAUNDERS, Ann M.; JAGER, Philip L. De; BARNES, Lisa L.; SCHNEIDER, Julie A.; BENNETT, David A.Introduction: The study investigated the role of neuropathologies in the relationship between TOMM40' 523 genotype and late-life cognitive decline. Methods: Participants were community-dwelling older persons who had annual cognitive assessments and brain autopsies after death. Genotyping used DNA from peripheral blood or postmortem brain tissue. Linear mixed models assessed the extent to which the association of '523 genotype with cognitive decline is attributable to neuropathologies. Results: Relative to epsilon 3/epsilon 3 homozygotes with '523-S/VL or '523-VL/VL genotype, both '523-L carriers and epsilon 3/epsilon 3 homozygotes with '523-S/S genotype had faster cognitive decline. The association of '523-L with cognitive decline was attenuated and no longer significant after controlling for Alzheimer's and other neuropathologies. By contrast, the association of '523-S/S was unchanged. Discussion: There are two distinct TOMM40' 523 signals in relation to late-life cognitive decline. One signal primarily acts through AD and other common neuropathologies, whereas the other operates through a different mechanism.