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Translational neuroscience of Alzheimer's disease: preclinical and clinical studies of b-amyloid peptide and other biomarkers

Abstract

The diagnosis of Alzheimer's disease (AD), a great public health problem, is imprecise and delayed (since the neurodegenerative processes begin years before the appearance of symptoms). The validation of AD biomarkers has the potential to afford early diagnosis and novel treatments. This project aims to investigate, in a multidisciplinary and translational fashion, the accumulation of b-amyloid peptide (the pathological hallmark of AD) and its associated brain changes (macroscopic and molecular), bringing together several 1A-B CNPq scientists and other researchers, members of 11 post-graduate teaching areas (7 of which level 6-7 CAPES), distributed across four centers of the Universidade de São Paulo - Faculdade de Medicina da USP (FMUSP), Faculdade de Medicina de Ribeirão Preto (FMRP), Instituto de Ciências Biomédicas (ICB) and Instituto de Psicologia (IP). We will carry out clinical studies with large samples, and these will be integrated with basic neuroscience investigations aimed at detailing the molecular processes underlying biomarker changes associated with the progression of AD and its treatment. These studies will involve: the use, for the first time in Brazil, of the b-amyloid tracer 11 C-PIB with positron emission tomography (PET); studies on healthy and pathological brain aging integrating the FMUSP-FMRP groups and evaluating 500 elderly individuals (subjects with minor cognitive impairment, AD and healthy controls) using magnetic resonance imaging and other biomarkers (cerebrospinal fluid / blood); application of novel pattern recognition methods for the extraction of statistical data evaluating the relative value of different biomarkers in regard to diagnostic accuracy, thus helping to delineate individualized "neurobiological signatures", within a perspective of personalized Medicine; and experiments with animal models and cell cultures investigating the impact of the exposure to b-amyloid in the brain, as well as changes in associated biochemical and electrophysiological processes. By endorsing the interaction of this group of scientists in the short and long term, we aim to increase the impact of our publications, pave the way for innovative drug trials with disease-modifying agents, and promote technological innovation in terms of diagnostic processes and patenting of novel pharmacological agents. (AU)

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Scientific publications (18)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RZEZAK, PATRICIA; LIMA, ELLEN MARISE; GARGARO, ANA CAROLINA; COIMBRA, ERICA; DE VINCENTIIS, SILVIA; VELASCO, TONICARLO RODRIGUES; LEITE, JOAO PEREIRA; BUSATTO, GERALDO F.; VALENTE, KETTE D.. Everyday memory impairment in patients with temporal lobe epilepsy caused by hippocampal sclerosis. Epilepsy & Behavior, v. 69, p. 31-36, . (12/09025-3, 12/50329-6, 13/11361-4, 12/13065-0)
SONVENSO, DANIELE KANASHIRO; ITIKAWA, EMERSON NOBUYUKI; SANTOS, MARCELO VOLPON; SANTOS, LEONARDO ALEXANDRE; TREVISAN, ANA CAROLINA; BIANCHIN, MARINO MUXFELDT; PITELLA, FELIPE ARRIVA; KATO, MERY; CARLOTTI, JR., CARLOS GILBERTO; FILHO BUSATTO, GERALDO; et al. Systematic review of the efficacy in seizure control and safety of neuronavigation in epilepsy surgery: The need for well-designed prospective studies. SEIZURE-EUROPEAN JOURNAL OF EPILEPSY, v. 31, p. 99-107, . (12/50329-6)
RZEZAK, PATRICIA; SQUARZONI, PAULA; DURAN, FABIO L.; FERRAZ ALVES, TANIA DE TOLEDO; TAMASHIRO-DURAN, JAQUELINE; BOTTINO, CASSIO M.; RIBEIZ, SALMA; LOTUFO, PAULO A.; MENEZES, PAULO R.; SCAZUFCA, MARCIA; et al. Relationship between Brain Age-Related Reduction in Gray Matter and Educational Attainment. PLoS One, v. 10, n. 10, . (13/03231-3, 12/50329-6, 12/13065-0)
SQUARZONI, PAULA; FARIA, DANIELE DE PAULA; YASSUDA, MONICA SANCHES; DE GOBBI PORTO, FABIO HENRIQUE; COUTINHO, ARTUR MARTINS; DA COSTA, NAOMI ANTUNES; NITRINI, RICARDO; FORLENZA, ORESTES VICENTE; DE SOUZA DURAN, FABIO LUIZ; DOZZI BRUCKI, SONIA MARIA; et al. Relationship Between PET-Assessed Amyloid Burden and Visual and Verbal Episodic Memory Performance in Elderly Subjects. JOURNAL OF ALZHEIMER'S DISEASE, v. 78, n. 1, p. 229-244, . (14/50873-3, 12/50329-6)
SIMON, SHARON S.; HAMPSTEAD, BENJAMIN M.; NUCCI, MARIANA P.; DURAN, FABIO L. S.; FONSECA, LUCIANA M.; MARTIN, MARIA DA GRACA M.; AVILA, RENATA; PORTO, FABIO H. G.; BRUCKI, SONIA M. D.; MARTINS, CAMILA B.; et al. Training gains and transfer effects after mnemonic strategy training in mild cognitive impairment: A fMRI study. INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY, v. 154, p. 15-26, . (12/50010-0, 12/50329-6, 12/51699-1)
CAROLINE CRISTIANO REAL; CLÁUDIA KIMIE SUEMOTO; KARINA HENRIQUE BINDA; LEA TENENHOLZ GRINBERG; CARLOS AUGUSTO PASQUALUCCI; WILSON JACOB FILHO; RENATA ELOAH DE LUCENA FERRETTI-REBUSTINI; RICARDO NITRINI; RENATA ELAINE PARAIZO LEITE; LUIZ ROBERTO DE BRITTO. O ESTILO DE VIDA ATIVO MELHORA O PERFIL DE EXPRESSÃO DE PROTEÍNAS EM INDIVÍDUOS COM A PATOLOGIA DE CORPOS DE LEWY. Dement. Neuropsychol., v. 15, n. 1, p. 41-50, . (16/16166-3, 12/50329-6, 13/25049-2)
LUIZ K. FERREIRA; JANE M. RONDINA; RODRIGO KUBO; CARLA R. ONO; CLAUDIA C. LEITE; JERUSA SMID; CASSIO BOTTINO; RICARDO NITRINI; GERALDO F. BUSATTO; FABIO L. DURAN; et al. Support vector machine-based classification of neuroimages in Alzheimer’s disease: direct comparison of FDG-PET, rCBF-SPECT and MRI data acquired from the same individuals. Revista Brasileira de Psiquiatria, v. 40, n. 2, p. 181-191, . (12/50329-6, 04/05551-6)
FERREIRA, LUIZ KOBUTI; BROCANELLO REGINA, ANA CAROLINA; KOVACEVIC, NATASA; MORAIS MARTIN, MARIA DA GRACA; SANTOS, PEDRO PAIM; CARNEIRO, CAMILA DE GODOI; KERR, DANIEL SHIKANAI; AMARO, JR., EDSON; MCINTOSH, ANTHONY RANDAL; BUSATTO, GERALDO F.. Aging Effects on Whole-Brain Functional Connectivity in Adults Free of Cognitive and Psychiatric Disorders. CEREBRAL CORTEX, v. 26, n. 9, p. 3851-3865, . (12/50329-6, 12/11898-5, 11/00475-3, 10/17083-8)
RZEZAK, PATRICIA; LIMA, ELLEN MARISE; PEREIRA, FABRICIO; GARGARO, ANA CAROLINA; COIMBRA, ERICA; DE VINCENTIIS, SILVIA; VELASCO, TONICARLO RODRIGUES; LEITE, JOAO PEREIRA; BUSATTO, GERALDO F.; VALENTE, KETTE D.. Decision-making in patients with temporal lobe epilepsy: Delay gratification ability is not impaired in patients with hippocampal sclerosis. Epilepsy & Behavior, v. 60, p. 158-164, . (12/09025-3, 12/50329-6, 13/11361-4, 12/13065-0)
CECCHINI, MARIO AMORE; YASSUDA, MONICA SANCHES; SQUARZONI, PAULA; COUTINHO, ARTUR MARTINS; FARIA, DANIELE DE PAULA; DE SOUZA DURAN, FABIO LUIZ; DA COSTA, NAOMI ANTUNES; DE GOBBI PORTO, FABIO HENRIQUE; NITRINI, RICARDO; FORLENZA, ORESTES VICENTE; et al. Deficits in short-term memory binding are detectable in individuals with brain amyloid deposition in the absence of overt neurodegeneration in the Alzheimer's disease continuum. BRAIN AND COGNITION, v. 152, . (14/50873-3, 16/50197-3, 12/50329-6, 16/07967-2)
GUIMARAES MARQUES, MARCIA JONATHAS; REAL, CAROLINE CRISTIANO; VICTORINO, DANIELLA BALDUINO; BRITTO, LUIZ ROBERTO; CAVALHEIRO, ESPER ABRAO; SCORZA, FULVIO ALEXANDRE; FERRAZ, HENRIQUE BALLALAI; SCORZA, CARLA ALESSANDRA. Endogenous protection against the 6-OHDA model of Parkinson's disease in the Amazonian rodent Proechimys. Neuroscience Letters, v. 709, . (16/06879-2, 12/50329-6, 13/25049-2, 16/17746-3)
LUÍS GUSTAVO RIBEIRO; GERALDO BUSATTO FILHO. MORFOMETRIA BASEADA EM VOXEL EM DOENÇA DE ALZHEIMER E COMPROMETIMENTO COGNITIVO LEVE: REVISÃO SISTEMÁTICA DE ESTUDOS ABORDANDO O LOBO FRONTAL. Dement. Neuropsychol., v. 10, n. 2, p. 104-112, . (12/50329-6)
BUSATTO FILHO, GERALDO; ROSA, PEDRO G.; SERPA, MAURICIO H.; SQUARZONI, PAULA; DURAN, FABIO L.. Psychiatric neuroimaging research in Brazil: historical overview, current challenges, and future opportunities. Revista Brasileira de Psiquiatria, v. 43, n. 1, p. 83-101, . (12/50329-6)
SIMON, SHARON S.; HAMPSTEAD, BENJAMIN M.; NUCCI, MARIANA P.; DURAN, FABIO L. S.; FONSECA, LUCIANA M.; MARTINO, MARIA DA GRACA M.; AVILA, RENATA; PORTO, FABIO H. G.; BRUCKI, SONIA M. D.; MARTINS, CAMILA B.; et al. Cognitive and Brain Activity Changes After Mnemonic Strategy Training in Amnestic Mild Cognitive Impairment: Evidence From a Randomized Controlled Tria. FRONTIERS IN AGING NEUROSCIENCE, v. 10, . (12/50329-6, 12/50010-0, 12/51699-1)
TASCONE, LYSSANDRA DOS SANTOS; PAYNE, MARTHA E.; MACFALL, JAMES; AZEVEDO, DIONISIO; DE CASTRO, CLAUDIO CAMPI; STEFFENS, DAVID C.; BUSATTO, GERALDO F.; BOTTINO, CASSIO M. C.. Cortical brain volume abnormalities associated with few or multiple neuropsychiatric symptoms in Alzheimer's disease. PLoS One, v. 12, n. 5, . (12/50329-6)
FERREIRA, LUIZ K.; RONDINA, JANE M.; KUBO, RODRIGO; ONO, CARLA R.; LEITE, CLAUDIA C.; SMID, JERUSA; BOTTINO, CASSIO; NITRINI, RICARDO; BUSATTO, GERALDO F.; DURAN, FABIO L.; et al. Support vector machine-based classification of neuroimages in Alzheimer's disease: direct comparison of FDG-PET, rCBF-SPECT and MRI data acquired from the same individuals. Revista Brasileira de Psiquiatria, v. 40, n. 2, p. 181-191, . (12/50329-6, 04/05551-6)

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