CARLOS AUGUSTO GONCALVES PASQUALUCCI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
ATCIENT-50, SVOC
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina - Líder
ATCIENT-50, SVOC
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina - Líder
12 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 12
- Neuropathologic Findings in a Patient With Juvenile-Onset Levodopa-Responsive Parkinsonism Due to ATP13A2 Mutation(2021) CHIEN, Hsin Fen; RODRIGUEZ, Roberta Diehl; BONIFATI, Vincenzo; NITRINI, Ricardo; PASQUALUCCI, Carlos Augusto; GELPI, Ellen; BARBOSA, Egberto ReisObjective To describe the postmortem neuropathologic findings of a patient with Kufor Rakeb syndrome (KRS) due to ATP13A2 mutation. KRS is characterized by juvenile-onset levodopa-responsive parkinsonism associated with pyramidal signs, supranuclear gaze palsy, and cognitive impairment. Methods A detailed neuropathologic analysis of the brain was performed. The patient had a genetically confirmed ATP13A2 homozygous missense mutation and died at age 38 years, which was 26 years after the onset of his symptoms. Results The main brain neuropathologic findings were widespread neuronal and glial lipofuscin accumulation with no Lewy body-type inclusions and absence of alpha-synuclein-positive, tau-positive, beta-amyloid-positive, and TDP-43 protein-positive pathologies. Sparse iron deposits were observed in several brain areas, but no obvious axonal spheroids were identified. Discussion This is to our knowledge the first KRS postmortem neuropathologic description. Iron deposits were found but not associated with increased axonal spheroids, as frequently observed in neurodegeneration with brain iron accumulation. ATP13A2 mutations have been described in patients with neuronal ceroid lipofuscinosis (CLN). Moreover, animal models with these mutations develop neurodegenerative disorders with CLN pathology. Therefore, our findings support that ATP13A2 mutations may be considered a genetic etiology of neuronal lipofuscinosis.
- Extracellular Matrix Proteome Remodeling in Human Glioblastoma and Medulloblastoma(2021) TROMBETTA-LIMA, Marina; ROSA-FERNANDES, Livia; ANGELI, Claudia B.; MORETTI, Isabele F.; FRANCO, Yollanda M.; MOUSESSIAN, Adaliana S.; WAKAMATSU, Alda; LERARIO, Antonio M.; OBA-SHINJO, Sueli M.; PASQUALUCCI, Carlos A.; MARIE, Suely K. N.; PALMISANO, GiuseppeMedulloblastomas (MBs) and glioblastomas (GBMs) are high-incidence central nervous system tumors. Different origin sites and changes in the tissue microenvironment have been associated with the onset and progression. Here, we describe differences between the extracellular matrix (ECM) signatures of these tumors. We compared the proteomic profiles of MB and GBM decellularized tumor samples between each other and their normal decellularized brain site counterparts. Our analysis revealed that 19, 28, and 11 ECM proteins were differentially expressed in MBs, GBMs, and in both MBs and GBMs, respectively. Next, we validated key findings by using a protein tissue array with 53 MB and 55 GBM cases and evaluated the clinical relevance of the identified differentially expressed proteins through their analysis on publicly available datasets, 763 MB samples from the GSE50161 and GSE85217 studies, and 115 GBM samples from RNAseq-TCGA. We report a shift toward a denser fibrillary ECM as well as a clear alteration in the glycoprotein signature, which influences the tumor pathophysiology.
conferenceObject TH1 lymphocytes in the perivascular adipose tissue correlate with plaque composition and increase the risk of intraplaque haemorrhages in coronary arteries: an autopsy study(2021) FARIAS-ITAO, D. S.; PASQUALUCCI, C. A.; ANDRADE, R. A.; SILVA, L. F. F.; ESTEVAM, M. Y.; CAMPO, A. B.; SUEMOTO, C. K.- Are the 50's, the transition decade, in choroid plexus aging?(2021) TAHIRA, Ana; MARQUES, Fernanda; LISBOA, Bianca; FELTRIN, Arthur; BARBOSA, Andre; OLIVEIRA, Katia Cristina de; PEREIRA, Carlos Alberto de Braganca; LEITE, Renata; GRINBERG, Lea; SUEMOTO, Claudia; FERRETTI-REBUSTINI, Renata Eloah de Lucena; PASQUALUCCI, Carlos Augusto; JACOB-FILHO, Wilson; BRENTANI, Helena; PALHA, Joana AlmeidaThe choroid plexus (CP) is an important structure for the brain. Besides its major role in the production of cerebrospinal fluid (CSF), it conveys signals originating from the brain, and from the circulatory system, shaping brain function in health and in pathology. Previous studies in rodents have revealed altered transcriptome both during aging and in various diseases of the central nervous system, including Alzheimer's disease. In the present study, a high-throughput sequencing of the CP transcriptome was performed in postmortem samples of clinically healthy individuals aged 50's through 80's. The data shows an age-related profile, with the main changes occurring in the transition from the 50's to the 60's, stabilizing thereafter. Specifically, neuronal and membrane functions distinguish the transcriptome between the 50's and the 60's, while neuronal and axon development and extracellular structure organization differentiate the 50's from the 70's. These findings suggest that changes in the CP transcriptome occur early in the aging process. Future studies will unravel whether these relate with processes occurring in late- onset brain diseases.
conferenceObject Increased Ratio of B2/B1-like Lymphocytes in the Perivascular Adipose Tissue Could Contribute to Plaque Destabilization in Human Coronary Arteries: Preliminary Results(2021) FARIAS-ITAO, Daniela S.; PASQUALUCCI, Carlos Augusto; ANDRADE, Renato A.; SILVA, Luiz Fernando F. Da; ESTEVAM, Maristella Y.; CAMPO, Alexandre B.; SUEMOTO, Claudia K.- Alcohol Use Disorder is Associated with Upregulation of MicroRNA-34a and MicroRNA-34c in Hippocampal Postmortem Tissue(2021) SANTOS-BEZERRA, Daniele P.; CAVALEIRO, Ana Mercedes; SANTOS, Aritania Sousa; SUEMOTO, Claudia Kimie; PASQUALUCCI, Carlos Augusto; JACOB-FILHO, Wilson; LEITE, Renata Elaine Paraizo; PASSARELLI, Marisa; MARIE, Suely Kazue Nagahashi; MACHADO, Ubiratan Fabres; CORREA-GIANNELLA, Maria LuciaBackground: To investigate epigenetic mechanisms potentially involved in the cognitive decline associated with chronic alcohol intake, we evaluated the expressions of three micro-RNAs (miR-34a, 34b, and -34c) highly expressed in the hippocampus and involved in neuronal physiology and pathology. MiR-34a participates in functioning and survival of mature neurons; miR-34b is associated with Alzheimer-like disorders; and miR-34c is implicated in the memory impairment of Alzheimer disease in rodents and humans. Methods: A total of 69 cases were selected from the Biobank for Aging Studies and categorized according to the absence (n = 50) or presence (n = 19) of alcohol use disorder (AUD). Cases presenting with neuropathological diagnoses of dementias were excluded. Total RNA was extracted from hippocampal paraffinized slices, complementary DNA was synthesized from miRs, and RT-qPCR was performed with TaqMan (R) assays. Results: Higher expressions of miR-34a and miR-34c, but not of miR-34b, were found in the group with AUD in comparison with the group without AUD after adjustment for potential confounders (age, sex, body mass index, presence of hypertension, diabetes mellitus, smoking, and physical inactivity). Conclusions: Hippocampal upregulation of miR-34a and miR-34c may be involved in the cognitive decline associated with chronic alcohol consumption.
conferenceObject Markers of inflammation and neurodegeneration in bipolar disorder older adults(2021) NASCIMENTO, Camila; NUNES, Paula; SUEMOTO, Claudia K.; RODRIGUEZ, Roberta D.; LEITE, Renata E. P.; GRINBERG, Lea; PASQUALUCCI, Carlos Augusto; JACOB-FILHO, Wilson; NITRINI, Ricardo; BRENTANI, Helena Paula; LAFER, Beny- Molecular characterization of selectively vulnerable neurons in Alzheimer's disease(2021) LENG, Kun; LI, Emmy; ESER, Rana; PIERGIES, Antonia; SIT, Rene; TAN, Michelle; NEFF, Norma; LI, Song Hua; RODRIGUEZ, Roberta Diehl; SUEMOTO, Claudia Kimie; LEITE, Renata Elaine Paraizo; EHRENBERG, Alexander J.; PASQUALUCCI, Carlos A.; SEELEY, William W.; SPINA, Salvatore; HEINSEN, Helmut; GRINBERG, Lea T.; KAMPMANN, MartinLeng et al. uncover the molecular signature of neuronal subpopulations that are selectively vulnerable to tau aggregation and death early in Alzheimer's disease in the human entorhinal cortex and other brain regions, validating RORB as a marker. Alzheimer's disease (AD) is characterized by the selective vulnerability of specific neuronal populations, the molecular signatures of which are largely unknown. To identify and characterize selectively vulnerable neuronal populations, we used single-nucleus RNA sequencing to profile the caudal entorhinal cortex and the superior frontal gyrus-brain regions where neurofibrillary inclusions and neuronal loss occur early and late in AD, respectively-from postmortem brains spanning the progression of AD-type tau neurofibrillary pathology. We identified RORB as a marker of selectively vulnerable excitatory neurons in the entorhinal cortex and subsequently validated their depletion and selective susceptibility to neurofibrillary inclusions during disease progression using quantitative neuropathological methods. We also discovered an astrocyte subpopulation, likely representing reactive astrocytes, characterized by decreased expression of genes involved in homeostatic functions. Our characterization of selectively vulnerable neurons in AD paves the way for future mechanistic studies of selective vulnerability and potential therapeutic strategies for enhancing neuronal resilience.
- beta-amyloid pathology is not associated with depression in a large community sample autopsy study(2021) SALDANHA, Nanci Moreira; SUEMOTO, Claudia Kimie; RODRIGUEZ, Roberta Diehl; LEITE, Renata Elaine Paraizo; NASCIMENTO, Camila; FERRETI-REBUSTINI, Renata; SILVA, Magnolia Moreira da; PASQUALUCCI, Carlos Augusto; NITRINI, Ricardo; JACOB-FILHO, Wilson; LAFER, Beny; GRINBERG, Lea T.; NUNES, Paula VillelaBackground: : Depression has been associated with dementia. This study aimed to verify if 13-amyloid Alzheimer's disease-type burden was associated with lifetime major depressive disorder (MDD) and with current depressive symptoms in a large population-based autopsy study. Methods: : We included 1013 deceased subjects submitted to autopsy (mean age=74.3 +/- 11.6 years, 49% men) in a community sample. 13-amyloid burden was measured in all cases based on the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria for presence and density of neuritic plaques. Lifetime MDD was defined when at least one previous episode according to the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders - DSM (SCID). Depressive symptoms and cognitive impairment were determined using the depression item of the Neuropsychiatric Inventory (D-NPI>0) and the Clinical Dementia Rating scale (CDR>0.5) respectively. Results: : Lifetime MDD, late life depression (LLD) and current depressive symptoms were associated with cognitive impairment (p<0.001). Additionally, neuritic plaques were associated with cognitive impairment (p<0.001). Moderate or frequent neurite plaque density was not associated with MDD, LLD or current depressive symptoms in multiple logistic models adjusted for age, gender, and cognitive impairment. Limitations:: In this cross-sectional study, all neuropsychiatric and cognitive assessment were based on informant-report of deceased participants. Conclusions: : Different clinical depictions of depression were associated with dementia in this large community sample of elderly individuals with multiethnic backgrounds. Notwithstanding, they were unrelated to 13-amyloid pathology in the brain areas studied. The link between depression and dementia might be complex and determined by multiple factors.
- Active lifestyle enhances protein expression profile in subjects with Lewy body pathology(2021) REAL, Caroline Cristiano; SUEMOTO, Cláudia Kimie; BINDA, Karina Henrique; GRINBERG, Lea Tenenholz; PASQUALUCCI, Carlos Augusto; JACOB FILHO, Wilson; FERRETTI-REBUSTINI, Renata Eloah de Lucena; NITRINI, Ricardo; LEITE, Renata Elaine Paraizo; BRITTO, Luiz Roberto deABSTRACT. Clinical trials of the effects of physical activity have reported improvements in symptoms and quality of life in patients with Parkinson's disease (PD). Additionally, morphological brain changes after exercising were reported in PD animal models. However, these lifestyle-related changes were not evaluated in postmortem brain tissue. Objective: We aimed to evaluate, by immunohistochemistry, astrocytes, tyrosine hydroxylase (TH) and structural proteins expression (neurofilaments and microtubules — MAP2) changes in postmortem brain samples of individuals with Lewy body pathology. Methods: Braak PD stage≥III samples, classified by neuropathology analysis, from The Biobank for Aging Studies were classified into active (n=12) and non-active (n=12) groups, according to physical activity lifestyle, and paired by age, sex and Braak staging. Substantia nigra and basal ganglia were evaluated. Results: Groups were not different in terms of age or gender and had similar PD neuropathological burden (p=1.00). We observed higher TH expression in the active group in the substantia nigra and the basal ganglia (p=0.04). Astrocytes was greater in the non-active subjects in the midbrain (p=0.03) and basal ganglia (p=0.0004). MAP2 levels were higher for non-active participants in the basal ganglia (p=0.003) and similar between groups in the substantia nigra (p=0.46). Neurofilament levels for non-active participants were higher in the substantia nigra (p=0.006) but not in the basal ganglia (p=0.24). Conclusion: Active lifestyle seems to promote positive effects on brain by maintaining dopamine synthesis and structural protein expression in the nigrostriatal system and decrease astrogliosis in subjects with the same PD neuropathology burden.