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
16 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 16
- 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.
- Trace element concentration differences in regions of human brain by INAA(2013) SAIKI, M.; LEITE, R. E. P.; GENEZINI, F. A.; GRINBERG, L. T.; FERRETTI, R. E. L.; FARFEL, J. M.; SUEMOTO, C.; PASQUALUCCI, C. A.; JACOB-FILHO, W.Studies have shown that there is a potential relationship between the levels of trace elements in cerebral tissues and neurological disorders. However, there are few publications available on the elemental composition of these tissues as well as for different regions of the brain. The aim of this study was to investigate trace element differences in various regions of the human brain from an elderly population of normal individuals. Brain samples from 31 individuals of both genders, aged 51-95 years were provided by the Brain Bank of the Brazilian Aging Study Group of the So Paulo University, Medical School. The tissues from the regions of the hippocampus, cerebellum and frontal, parietal, temporal, occipital cortex were dissected using a titanium knife, ground, freeze-dried and then analyzed by instrumental neutron activation analysis (INAA). Samples and element standards were irradiated with a neutron flux at the IEA-R1 nuclear research reactor for Br, Fe, K, Na, Rb, Se and Zn determinations. One-way ANOVA test (p < 0.05) was used to compare the results which showed significant differences for several elements among the brain regions. Most of our brain analysis results agreed with the literature data. The results were also submitted for brain region classification by cluster analysis.
- 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.
- Is Olfactory Epithelium Biopsy Useful for Confirming Alzheimer's Disease?(2019) GODOY, Maria Dantas Costa Lima; FORNAZIERI, Marco Aurelio; DOTY, Richard L.; PINNA, Fabio de Rezende; FARFEL, Jose Marcelo; SANTOS, Glaucia Bento dos; MOLINA, Mariana; FERRETTI-REBUSTINI, Renata E. L.; LEITE, Renata E. P.; SUEMOTO, Claudia K.; GRINBERG, Lea T.; PASCRALUCCI, Carlos A. G.; VOEGELS, Richard Louis; NITRINI, Ricardo; JACOB FILHO, WilsonObjectives: The clinical symptoms of Alzheimer's disease (AD) are preceded by a long asymptomatic period associated with ""silent"" deposition of aberrant paired helical filament (PHF)-tau and amyloid-beta proteins in brain tissue. Similar depositions have been reported within the olfactory epithelium (OE), a tissue that can be biopsied in vivo. The degree to which such biopsies are useful in identifying AD is controversial. This postmortem study had 3 main goals: first, to quantify the relative densities of AD-related proteins in 3 regions of the olfactory neuroepithelium, namely, the nasal septum, middle turbinate, and superior turbinate; second, to establish whether such densities are correlated among these epithelial regions as well as with semi-quantitative ratings of general brain cortex pathology; and third, to evaluate correlations between the protein densities and measures of antemortem cognitive function. Methods: Postmortem blocks of olfactory mucosa were obtained from 12 AD cadavers and 24 controls and subjected to amyloid-beta and PHF-tau immunohistochemistry. Results: We observed marked heterogeneity in the presence of the biomarkers of tau and amyloid-beta among the targeted olfactory epithelial regions. No significant difference was observed between the cadavers with AD and the controls regarding the concentration of these proteins in any of these epithelial regions. Only one correlation significant was evident, namely, that between the tau protein densities of the middle and the upper turbinate (r = .58, P = .002). Conclusion: AD-related biomarker heterogeneity, which has not been previously demonstrated, makes comparisons across studies difficult and throws into question the usefulness of OE amyloid-beta and PHF-tau biopsies in detecting AD.
- 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.)
- Association of APOE with tau-tangle pathology with and without beta-amyloid(2016) FARFEL, Jose M.; YU, Lei; JAGER, Philip L. De; SCHNEIDER, Julie A.; BENNETT, David A.This study tested the hypothesis that the association of apolipoprotein E (APOE) with paired helical filament tau (PHF-tau) tangle pathology differs in brains with and without beta-amyloid. Participants were 1056 autopsied individuals from 2 clinical-pathologic cohort studies of aging and Alzheimer's disease (AD), the Religious Orders Study, and the Rush Memory and Aging Project. Neuropathologic measures were obtained using immunohistochemistry targeting beta-amyloid and PHF-tau tangles in 8 brain regions. Linear regression was used to compare the relation of APOE epsilon 4 and epsilon 2 to PHF-tau-tangle density in persons with beta-amyloid relative to persons without beta-amyloid. We found an interaction between APOE epsilon 4 carriers and presence of beta-amyloid (beta = -0.968, p = 0.013) such that the association of APOE epsilon 4 with PHF-tau tangles was much stronger in brains with beta-amyloid. Stratified analysis shows that the association of APOE epsilon 4 with PHF-tau tangles was considerably stronger among those with beta-amyloid (beta = 0.757, p = 1.1 x 10(-15)) compared to those without beta-amyloid which was not significant (beta = -0.201, p = 0.424). Separately, APOE epsilon 2 was associated with fewer tangles in brains with beta-amyloid (beta = -0.425, p = 7.6 x 10(-4)) compared to those without beta-amyloid which was not significant (beta = -0.102, p = 0.506). Thus, the presence of APOE epsilon 4 and epsilon 2 alleles was not associated with PHF-tau tangles in the absence of beta-amyloid. The data provide additional evidence that PHF-tau tangles in the absence of beta-amyloid may reflect a pathologic process distinct from Alzheimer's disease.
- 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.
- Estimating Premorbid Cognitive Abilities in Low-Educated Populations(2013) APOLINARIO, Daniel; BRUCKI, Sonia Maria Dozzi; FERRETTI, Renata Eloah de Lucena; FARFEL, Jose Marcelo; MAGALDI, Regina Miksian; BUSSE, Alexandre Leopold; JACOB-FILHO, WilsonObjective: To develop an informant-based instrument that would provide a valid estimate of premorbid cognitive abilities in low-educated populations. Methods: A questionnaire was drafted by focusing on the premorbid period with a 10-year time frame. The initial pool of items was submitted to classical test theory and a factorial analysis. The resulting instrument, named the Premorbid Cognitive Abilities Scale (PCAS), is composed of questions addressing educational attainment, major lifetime occupation, reading abilities, reading habits, writing abilities, calculation abilities, use of widely available technology, and the ability to search for specific information. The validation sample was composed of 132 older Brazilian adults from the following three demographically matched groups: normal cognitive aging (n = 72), mild cognitive impairment (n = 33), and mild dementia (n = 27). The scores of a reading test and a neuropsychological battery were adopted as construct criteria. Post-mortem inter-informant reliability was tested in a sub-study with two relatives from each deceased individual. Results: All items presented good discriminative power, with corrected item-total correlation varying from 0.35 to 0.74. The summed score of the instrument presented high correlation coefficients with global cognitive function (r = 0.73) and reading skills (r = 0.82). Cronbach's alpha was 0.90, showing optimal internal consistency without redundancy. The scores did not decrease across the progressive levels of cognitive impairment, suggesting that the goal of evaluating the premorbid state was achieved. The intraclass correlation coefficient was 0.96, indicating excellent inter-informant reliability. Conclusion: The instrument developed in this study has shown good properties and can be used as a valid estimate of premorbid cognitive abilities in low-educated populations. The applicability of the PCAS, both as an estimate of premorbid intelligence and cognitive reserve, is discussed.
- Alzheimer's disease frequency peaks in the tenth decade and is lower afterwards(2019) FARFEL, Jose M.; YU, Lei; BOYLE, Patricia A.; LEURGANS, Sue; SHAH, Raj C.; SCHNEIDER, Julie A.; BENNETT, David A.Age is the most robust risk factor for Alzheimer's dementia, however there is little data on the relation of age to Alzheimer's disease (AD) and other common neuropathologies that contribute to Alzheimer's dementia. We use data from two community-based, clinical-pathologic cohorts to examine the association of age with AD and other common pathologies. Participants were 1420 autopsied individuals from the Religious Orders Study or Rush Memory and Aging Project who underwent annual clinical evaluations for diagnosis of Alzheimer's dementia, mild cognitive impairment (MCI), and level of cognition. The neuropathologic traits of interest were pathologic AD according to modified NIA-Reagan criteria, three quantitative measures of AD pathology (global AD pathology score, beta-amyloid load and PHFtau tangle density), macro- and micro-scopic infarcts, neocortical Lewy bodies, TDP-43 and hippocampal sclerosis. Semiparametric generalized additive models examined the nonlinear relationship between age and the clinical and pathological outcomes. The probability of Alzheimer's dementia at death increased with age such that for every additional year of age, the log odds of Alzheimer's dementia was 0.067 higher, corresponding to an odds ratio of 1.070 (p<0.001). Results were similar for cognitive impairment and level of cognition. By contrast, a nonlinear relationship of age with multiple indices of AD pathology was observed (all ps<0.05), such that pathologic AD reached a peak around 95years of age and leveled off afterwards; the quantitative measures of AD pathology were significantly lower at ages above 95. The association of age with other neuropathologies was quite distinct from that of AD in that most increased with advancing age. AD pathology appears to peak around 95years of age while other common pathologies continue to increase with age.
- Olfaction in Neurologic and Neurodegenerative Diseases: A Literature Review(2015) GODOY, Maria Dantas Costa Lima; VOEGELS, Richard Louis; PINNA, Fábio de Rezende; IMAMURA, Rui; FARFEL, José MarceloIntroduction Loss of smell is involved in various neurologic and neurodegenerative diseases, such as Parkinson disease and Alzheimer disease. However, the olfactory test is usually neglected by physicians at large. Objective The aim of this study was to review the current literature about the relationship between olfactory dysfunction and neurologic and neurodegenerative diseases. Data Synthesis Twenty-seven studies were selected for analysis, and the olfactory system, olfaction, and the association between the olfactory dysfunction and dementias were reviewed. Furthermore, is described an up to date in olfaction. Conclusion Otolaryngologist should remember the importance of olfaction evaluation in daily practice. Furthermore, neurologists and physicians in general should include olfactory tests in the screening of those at higher risk of dementia.