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
5 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.
- Locus coeruleus volume and cell population changes during Alzheimer's disease progression: A stereological study in human postmortem brains with potential implication for early-stage biomarker discovery(2017) THEOFILAS, Panos; EHRENBERG, Alexander J.; DUNLOP, Sara; ALHO, Ana T. Di Lorenzo; NGUY, Austin; LEITE, Renata Elaine Paraizo; RODRIGUEZ, Roberta Diehl; MEJIA, Maria B.; SUEMOTO, Claudia K.; FERRETTI-REBUSTINI, Renata Eloah De Lucena; POLICHISO, Livia; NASCIMENTO, Camila F.; SEELEY, William W.; NITRINI, Ricardo; PASQUALUCCI, Carlos Augusto; JACOB FILHO, Wilson; RUEB, Udo; NEUHAUS, John; HEINSEN, Helmut; GRINBERG, Lea T.Introduction: Alzheimer's disease (AD) progression follows a specific spreading pattern, emphasizing the need to characterize those brain areas that degenerate first. The brainstem's locus coeruleus (LC) is the first area to develop neurofibrillary changes (neurofibrillary tangles [NFTs]). Methods: The methods include unbiased stereologiCal analyses in human brainstems to estimate LC volume and neuronal population in controls and individuals across all AD stages. Results: As the Braak stage increases by 1 unit, the LC volume decreases by 8.4%. Neuronal loss started only midway through AD progression. Age-related changes spare the LC. Discussion: The long gap between NFT accumulation and neuronal loss suggests that a second trigger may be necessary to induce neuronal death in AD. Imaging studies should determine whether LC volumetry can replicate the stage-wise atrophy observed here and how these changes are specific to AD. LC volumetry may develop into a screening biomarker for selecting high-yield candidates to undergo expensive and less accessible positron emission tomography scans and to monitor AD progression from presymptomatic stages.
- 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.
- 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.
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