ROBERTA DIEHL RODRIGUEZ
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Radiologia, Hospital das Clínicas, Faculdade de Medicina
LIM/44 - Laboratório de Ressonância Magnética em Neurorradiologia, Hospital das Clínicas, Faculdade de Medicina
LIM/44 - Laboratório de Ressonância Magnética em Neurorradiologia, Hospital das Clínicas, Faculdade de Medicina
12 resultados
Resultados de Busca
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- 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.
- Frequency of LATE neuropathologic change across the spectrum of Alzheimer's disease neuropathology: combined data from 13 community-based or population-based autopsy cohorts(2022) NELSON, Peter T.; BRAYNE, Carol; FLANAGAN, Margaret E.; ABNER, Erin L.; AGRAWAL, Sonal; ATTEMS, Johannes; CASTELLANI, Rudolph J.; CORRADA, Maria M.; CYKOWSKI, Matthew D.; DI, Jing; DICKSON, Dennis W.; DUGGER, Brittany N.; ERVIN, John F.; FLEMING, Jane; GRAFF-RADFORD, Jonathan; GRINBERG, Lea T.; HOKKANEN, Suvi R. K.; HUNTER, Sally; KAPASI, Alifiya; KAWAS, Claudia H.; KEAGE, Hannah A. D.; KEENE, C. Dirk; KERO, Mia; KNOPMAN, David S.; KOURI, Naomi; KOVACS, Gabor G.; LABUZAN, Sydney A.; LARSON, Eric B.; LATIMER, Caitlin S.; LEITE, Renata E. P.; MATCHETT, Billie J.; MATTHEWS, Fiona E.; MERRICK, Richard; MONTINE, Thomas J.; MURRAY, Melissa E.; MYLLYKANGAS, Liisa; NAG, Sukriti; NELSON, Ruth S.; NELTNER, Janna H.; NGUYEN, Aivi T.; PETERSEN, Ronald C.; POLVIKOSKI, Tuomo; REICHARD, R. Ross; RODRIGUEZ, Roberta D.; SUEMOTO, Claudia K.; WANG, Shih-Hsiu J.; WHARTON, Stephen B.; WHITE, Lon; SCHNEIDER, Julie A.Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and Alzheimer's disease neuropathologic change (ADNC) are each associated with substantial cognitive impairment in aging populations. However, the prevalence of LATE-NC across the full range of ADNC remains uncertain. To address this knowledge gap, neuropathologic, genetic, and clinical data were compiled from 13 high-quality community- and population-based longitudinal studies. Participants were recruited from United States (8 cohorts, including one focusing on Japanese-American men), United Kingdom (2 cohorts), Brazil, Austria, and Finland. The total number of participants included was 6196, and the average age of death was 88.1 years. Not all data were available on each individual and there were differences between the cohorts in study designs and the amount of missing data. Among those with known cognitive status before death (n = 5665), 43.0% were cognitively normal, 14.9% had MCI, and 42.4% had dementia-broadly consistent with epidemiologic data in this age group. Approximately 99% of participants (n = 6125) had available CERAD neuritic amyloid plaque score data. In this subsample, 39.4% had autopsy-confirmed LATE-NC of any stage. Among brains with ""frequent"" neuritic amyloid plaques, 54.9% had comorbid LATE-NC, whereas in brains with no detected neuritic amyloid plaques, 27.0% had LATE-NC. Data on LATE-NC stages were available for 3803 participants, of which 25% had LATE-NC stage > 1 (associated with cognitive impairment). In the subset of individuals with Thal A beta phase = 0 (lacking detectable A beta plaques), the brains with LATE-NC had relatively more severe primary age-related tauopathy (PART). A total of 3267 participants had available clinical data relevant to frontotemporal dementia (FTD), and none were given the clinical diagnosis of definite FTD nor the pathological diagnosis of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). In the 10 cohorts with detailed neurocognitive assessments proximal to death, cognition tended to be worse with LATE-NC across the full spectrum of ADNC severity. This study provided a credible estimate of the current prevalence of LATE-NC in advanced age. LATE-NC was seen in almost 40% of participants and often, but not always, coexisted with Alzheimer's disease neuropathology.
conferenceObject High prevalence of TDP-43 in Asians older adults: a clinicopathological study on a population-based sample(2014) NASCIMENTO, C.; RODRIGUEZ, R. D.; LEITE, R. P.; SUEMOTO, C. K.; ZATZ, M.; PASQUALUCCI, C. A.; FILHO, W. J.; GRINBERG, L. T.- 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.
- Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy(2016) KOVACS, Gabor G.; FERRER, Isidro; GRINBERG, Lea T.; ALAFUZOFF, Irina; ATTEMS, Johannes; BUDKA, Herbert; CAIRNS, Nigel J.; CRARY, John F.; DUYCKAERTS, Charles; GHETTI, Bernardino; HALLIDAY, Glenda M.; IRONSIDE, James W.; LOVE, Seth; MACKENZIE, Ian R.; MUNOZ, David G.; MURRAY, Melissa E.; NELSON, Peter T.; TAKAHASHI, Hitoshi; TROJANOWSKI, John Q.; ANSORGE, Olaf; ARZBERGER, Thomas; BABORIE, Atik; BEACH, Thomas G.; BIENIEK, Kevin F.; BIGIO, Eileen H.; BODI, Istvan; DUGGER, Brittany N.; FEANY, Mel; GELPI, Ellen; GENTLEMAN, Stephen M.; GIACCONE, Giorgio; HATANPAA, Kimmo J.; HEALE, Richard; HOF, Patrick R.; HOFER, Monika; HORTOBAGYI, Tibor; JELLINGER, Kurt; JICHA, Gregory A.; INCE, Paul; KOFLER, Julia; KOEVARI, Enikoe; KRIL, Jillian J.; MANN, David M.; MATEJ, Radoslav; MCKEE, Ann C.; MCLEAN, Catriona; MILENKOVIC, Ivan; MONTINE, Thomas J.; MURAYAMA, Shigeo; LEE, Edward B.; RAHIMI, Jasmin; RODRIGUEZ, Roberta D.; ROZEMULLER, Annemieke; SCHNEIDER, Julie A.; SCHULTZ, Christian; SEELEY, William; SEILHEAN, Danielle; SMITH, Colin; TAGLIAVINI, Fabrizio; TAKAO, Masaki; THAL, Dietmar Rudolf; TOLEDO, Jon B.; TOLNAY, Markus; TRONCOSO, Juan C.; VINTERS, Harry V.; WEIS, Serge; WHARTON, Stephen B.; III, Charles L. White; WISNIEWSKI, Thomas; WOULFE, John M.; YAMADA, Masahito; DICKSON, Dennis W.Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of astroglial tau pathology in the aged brain, facilitating communication among neuropathologists and researchers, and informing interpretation of clinical biomarkers and imaging studies that focus on tau-related indicators.
article 0 Citação(ões) na Scopus Cause of Death Determined by Full-body Autopsy in Neuropathologically Diagnosed Dementias The Biobank for Aging Studies of the University of Sao Paulo (BAS-USP), Brazil(2022) NEVES, Beatriz Astolfi; NUNES, Paula Villela; RODRIGUEZ, Roberta Diehl; HAIDAR, Atmis Medeiros; LEITE, Renata Elaine Paraizo; NASCIMENTO, Camila; PASQUALUCCI, Carlos Augusto; NITRINI, Ricardo; JACOB-FILHO, Wilson; LAFER, Beny; GRINBERG, Lea TenenholzObjective: This study aimed to compare causes of death in the most prevalent neuropathologically diagnosed dementias. Methods: We analyzed causes of death in a community-based cohort of participants aged 50 or older, submitted to full-body autopsy and a comprehensive neuropathologic examination of the brain. Individuals with Alzheimer disease (AD), vascular dementia (VaD), mixed dementia (AD+VaD), or dementia with Lewy bodies (DLBs) were compared with individuals with no dementia. Results: In a sample of 920 individuals, 456 had no dementia, 147 had AD, 120 had VaD, 53 had DLB, and 37 had AD+VaD. Pneumonia as the cause of death was more frequent in the AD (P= 0.023), AD+VaD (P= 0.046), and DLB (P= 0.043) groups. In addition, VaD (P= 0.041) and AD+VaD (P= 0.028) groups had a higher frequency of atherosclerosis as detected by full-body autopsy. Conclusion: Our findings highlight the importance of preventive measures regarding atherosclerosis and pneumonia in patients with dementia. Moreover, because of cognitive impairment, these patients may not fully account for symptoms to make early detection and diagnosis possible. These results confirm findings from previous studies that were based on clinical data, with added accuracy provided by neuropathologic diagnosis and full-body autopsy reports.- Multisite Assessment of Aging-Related Tau Astrogliopathy (ARTAG)(2017) KOVACS, Gabor G.; XIE, Sharon X.; LEE, Edward B.; ROBINSON, John L.; CASWELL, Carrie; IRWIN, David J.; TOLEDO, Jon B.; JOHNSON, Victoria E.; SMITH, Douglas H.; ALAFUZOFF, Irina; ATTEMS, Johannes; BENCZE, Janos; BIENIEK, Kevin F.; BIGIO, Eileen H.; BODI, Istvan; BUDKA, Herbert; DICKSON, Dennis W.; DUGGER, Brittany N.; DUYCKAERTS, Charles; FERRER, Isidro; FORREST, Shelley L.; GELPI, Ellen; GENTLEMAN, Stephen M.; GIACCONE, Giorgio; GRINBERG, Lea T.; HALLIDAY, Glenda M.; HATANPAA, Kimmo J.; HOF, Patrick R.; HOFER, Monika; HORTOBAGYI, Tibor; IRONSIDE, James W.; KING, Andrew; KOFLER, Julia; KOVARI, Eniko; KRIL, Jillian J.; LOVE, Seth; MACKENZIE, Ian R.; MAO, Qinwen; MATEJ, Radoslav; MCLEAN, Catriona; MUNOZ, David G.; MURRAY, Melissa E.; NELTNER, Janna; NELSON, Peter T.; RITCHIE, Diane; RODRIGUEZ, Roberta D.; ROHAN, Zdenek; ROZEMULLER, Annemieke; SAKAI, Kenji; SCHULTZ, Christian; SEILHEAN, Danielle; SMITH, Vanessa; TACIK, Pawel; TAKAHASHI, Hitoshi; TAKAO, Masaki; THAL, Dietmar Rudolf; WEIS, Serge; WHARTON, Stephen B.; III, Charles L. White; WOULFE, John M.; YAMADA, Masahito; TROJANOWSKI, John Q.Aging-related tau astrogliopathy (ARTAG) is a recently introduced terminology. To facilitate the consistent identification of ARTAG and to distinguish it from astroglial tau pathologies observed in the primary frontotemporal lobar degeneration tauopathies we evaluated how consistently neuropathologists recognize (1) different astroglial tau immunoreactivities, including those of ARTAG and those associated with primary tauopathies (Study 1); (2) ARTAG types (Study 2A); and (3) ARTAG severity (Study 2B). Microphotographs and scanned sections immunostained for phosphorylated tau (AT8) were made available for download and preview. Percentage of agreement and kappa values with 95% confidence interval (CI) were calculated for each evaluation. The overall agreement for Study 1 was > 60% with a kappa value of 0.55 (95% CI 0.433-0.645). Moderate agreement (> 90%, kappa 0.48, 95% CI 0.457-0.900) was reached in Study 2A for the identification of ARTAG pathology for each ARTAG subtype (kappa 0.37-0.72), whereas fair agreement (kappa 0.40, 95% CI 0.341-0.445) was reached for the evaluation of ARTAG severity. The overall assessment of ARTAG showed moderate agreement (kappa 0.60, 95% CI 0.534-0.653) among raters. Our study supports the application of the current harmonized evaluation strategy for ARTAG with a slight modification of the evaluation of its severity.
- GRN and MAPT Mutations in 2 Frontotemporal Dementia Research Centers in Brazil(2016) TAKADA, Leonel T.; BAHIA, Valeria S.; GUIMARAES, Henrique C.; COSTA, Thais V. M. M.; VALE, Thiago C.; RODRIGUEZ, Roberta D.; PORTO, Fabio H. G.; MACHADO, Joao C. B.; BEATO, Rogerio G.; CESAR, Karolina G.; SMID, Jerusa; NASCIMENTO, Camila F.; GRINBERG, Lea T.; BRUCKI, Sonia M. D.; MAXIMINO, Jessica R.; CAMARGOS, Sarah T.; CHADI, Gerson; CARAMELLI, Paulo; NITRINI, RicardoBackground: Mutations in GRN (progranulin) and MAPT (microtubule-associated protein tau) are among the most frequent causes of monogenic frontotemporal dementia (FTD), but data on the frequency of these mutations in regions such as Latin America are still lacking. Objective: We aimed to investigate the frequencies of GRN and MAPT mutations in FTD cohorts from 2 Brazilian dementia research centers, the University of Sao Paulo and the Federal University of Minas Gerais medical schools. Methods: We included 76 probands diagnosed with behavioral-variant FTD (n = 55), semantic-variant Primary Progressive Aphasia (PPA) (n = 11), or nonfluent-variant PPA (n = 10). Twenty-five percent of the cohort had at least 1 relative affected with FTD. Results: Mutations in GRN were identified in 7 probands, and in MAPT, in 2 probands. We identified 3 novel GRN mutations (p.Q130X, p.317Afs*12, and p.K259Afs*23) in patients diagnosed with nonfluent-variant PPA or behavioral-variant FTD. Plasma progranulin levels were measured and a cutoff value of 70 ng/mL was found, with 100% sensitivity and specificity to detect null GRN mutations. Conclusions: The frequency of GRN mutations was 9.6% and that of MAPT mutations was 7.1%. Among familial cases of FTD, the frequency of GRN mutations was 31.5% and that of MAPT mutations was 10.5%.
- Neuropathological lesions in the very old: results from a large Brazilian autopsy study(2019) SUEMOTO, Claudia K.; LEITE, Renata E. P.; FERRETTI-REBUSTINI, Renata E. L.; RODRIGUEZ, Roberta D.; NITRINI, Ricardo; PASQUALUCCI, Carlos A.; JACOB-FILHO, Wilson; GRINBERG, Lea T.Objective To compare neuropathological correlates of cognitive impairment between very old and younger individuals from a Brazilian clinicopathological study. Methods We assessed the frequency of neuropathological lesions and their association with cognitive impairment (Clinical Dementia Rating scale >= 0.5) in the 80 or over age group compared to younger participants, using logistic regression models adjusted for sex, race and education. Results Except for infarcts and siderocalcinosis, all neuropathological lesions were more common in the 80 or over age group (n = 412) compared to 50-79 year olds (n = 677). Very old participants had more than twice the likelihood of having >= 2 neuropathological diagnoses than younger participants (OR = 2.66, 95% CI = 2.03-3.50). Neurofibrillary tangles, infarcts and hyaline arteriolosclerosis were associated with cognitive impairment in the two age groups. Siderocalcinosis was associated with cognitive impairment in the younger participants only, while Lewy body disease was associated with cognitive impairment in the very old only. In addition, we found that the association of infarcts and multiple pathologies with cognitive impairment was attenuated in very old adults (Infarcts: P for interaction = 0.04; and multiple pathologies: P = 0.05). However, the predictive value for the aggregate model with all neuropathological lesions showed similar discrimination in both age groups [Area under Receiver Operating Characteristic curve (AUROC) = 0.778 in younger participants and AUROC = 0.765 in the very old]. Conclusion and relevance Despite a higher frequency of neuropathological findings in the very old group, as found in studies with high-income populations, we found attenuation of the effect of infarcts rather than neurofibrillary tangles and plaques as reported previously.
conferenceObject Argyrophilic grain disease may delay cognitive decline in AD: an autopsy study(2015) GRINBERG, Lea; RODRIGUEZ, Roberta; SUEMOTO, Claudia; MOLINA, Mariana; NASCIMENTO, Camila; LEITE, Renata; FERRETTI-REBUSTINI, Renata; FARFEL, Jose; HEINSEN, Helmut; NITRINI, Ricardo; PASQUALLUCCI, Carlos; JACOB-FILHO, Wilson; YAFFE, Kristine