CAMILA NASCIMENTO MANTELLI
Projetos de Pesquisa
Unidades Organizacionais
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
- Prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults: systematic review and meta-analysis(2018) NASCIMENTO, C.; ALHO, A. T. Di Lorenzo; AMARAL, C. Bazan Conceicao; LEITE, R. E. P.; NITRINI, R.; JACOB-FILHO, W.; PASQUALUCCI, C. A.; HOKKANEN, S. R. K.; HUNTER, S.; KEAGE, H.; KOVACS, G. G.; GRINBERG, L. T.; SUEMOTO, C. K.ObjectiveTo perform a systematic review and meta-analysis on the prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults. MethodsWe systematically reviewed and performed a meta-analysis on the prevalence of TDP-43 proteinopathy in older adults with normal cognition, evaluated by the Mini-Mental State Examination or the Clinical Dementia Rating. We estimated the overall prevalence of TDP-43 using random-effect models, and stratified by age, sex, sample size, study quality, antibody used to assess TDP-43 aggregates, analysed brain regions, Braak stage, Consortium to Establish a Registry for Alzheimer's Disease score, hippocampal sclerosis and geographic location. ResultsA total of 505 articles were identified in the systematic review, and 7 were included in the meta-analysis with 1196 cognitively normal older adults. We found an overall prevalence of TDP-43 proteinopathy of 24%. Prevalence of TDP-43 proteinopathy varied widely across geographic location (North America: 37%, Asia: 29%, Europe: 14%, and Latin America: 11%). Estimated prevalence of TDP-43 proteinopathy also varied according to study quality (quality score >7: 22% vs. quality score <7: 42%), antibody used to assess TDP-43 proteinopathy (native: 18% vs. hyperphosphorylated: 24%) and presence of hippocampal sclerosis (without 24% vs. with hippocampal sclerosis: 48%). Other stratified analyses by age, sex, analysed brain regions, sample size and severity of AD neuropathology showed similar pooled TDP-43 prevalence. ConclusionsDifferent methodology to access TDP-43, and also differences in lifestyle and genetic factors across different populations could explain our results. Standardization of TDP-43 measurement, and future studies about the impact of genetic and lifestyle characteristics on the development of neurodegenerative diseases are needed.
- 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 Brain transcriptome analysis of Japanese population living in Brazil(2019) MARIE, Suely Kazue Nagahashi; LERARIO, Antonio Marcondes; SHINJO, Sueli Mieko Oba; NASCIMENTO, Camila; LEITE, Renata; SUEMOTO, Claudia; PASQUALUCCI, Carlos Augusto; MURAYAMA, Shigeo- 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.
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.- 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%.
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- Higher Prevalence of TDP-43 Proteinopathy in Cognitively Normal Asians: A Clinicopathological Study on a Multiethnic Sample(2016) NASCIMENTO, Camila; SUEMOTO, Claudia K.; RODRIGUEZ, Roberta D.; ALHO, Ana Tereza Di Lorenzo; LEITE, Renata P.; FARFEL, Jose Marcelo; PASQUALUCCI, Carlos Augusto Goncalves; JACOB-FILHO, Wilson; GRINBERG, Lea T.Transactive response DNA binding protein 43 (TDP-43) proteinopathy is the major hallmark of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. It is also present in a subset of Alzheimer's disease cases. Recently, few reports showed TDP-43 changes in cognitively normal elderly. In Caucasians, TDP-43 proteinopathy independently correlate with cognitive decline. However, it is challenging to establish direct links between cognitive and/or neuropsychiatric symptoms and protein inclusions in neurodegenerative diseases because individual cognitive reserves modify the threshold for clinical disease expression. Cognitive reserve is influenced by demographic, environmental and genetic factors. We investigated the relationships between demographic, clinical and neuropathological variables and TDP-43 proteinopathy in a large multiethnic sample of cognitively normal elderly. TDP-43 proteinopathy was identified in 10.5%, independently associated with older age (P=0.03) and Asian ethnicity (P=0.002). Asians showed a higher prevalence of TDP-43 proteinopathy than Caucasians, even after adjustment for sex, age, Braak stage and schooling (odds ratio=3.50, confidence interval 1.41-8.69, P=0.007). These findings suggested that Asian older adults may be protected from the clinical manifestation of brain TDP-43 proteinopathy. Future studies are needed to identify possible race-related protective factors against clinical expression of TDP-43 proteinopathies.