Translational neuroimaging in intellectual disability: evaluation of molecular changes associated with aging in Down Syndrome

• Grant number: 18/15167-1
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: February 01, 2019
• End date: January 31, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Radiology
• Agreement: Instituto Jô Clemente
• Principal Investigator: Daniele de Paula Faria
• Grantee: Daniele de Paula Faria
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Carlos Alberto Buchpiguel ; Caroline Cristiano Real Gregório ; Emerson Nobuyuki Itikawa ; Fábio Luís de Souza Duran ; Fabio Luiz Navarro Marques ; Geraldo Busatto Filho
• Associated scholarship(s): 22/06370-3 - Evaluation of the cannabidiol effect on the aging process of a transgenic Down syndrome model, BP.PD; 22/03623-8 - Evaluation of 11C-PK11195 metabolites in venous blood of people with Down Syndrome, BP.IC; 20/11728-9 - PET imaging for the evaluation of neuroinflammation in the aging of people with Down Syndrome, BP.MS; + associated scholarships 21/02272-4 - Evaluation of 11C-PK11195 metabolites in venous blood of people with Down Syndrome, BP.IC; 20/08015-0 - Behavioral and histological evaluation of an animal model of Down Syndrome, BP.IC; 19/15654-2 - Evaluation of molecular changes associated with aging in the Down Syndrome animal model, BP.DD - associated scholarships

Abstract

Down Syndrome (DS) or trisomy 21 is the most common genetic cause of mild to moderate intellectual disability in the world. The life expectancy of DS patients has increased in the last decades and, therefore, the incidence of dementia, especially Alzheimer's Disease (AD) increases in this population, making aging a new and important area of study in DS. Molecular neuroimaging allows in vivo and noninvasive studies of cellular and molecular processes, and therefore, is a very important tool to understand the aging process. This project proposes the creation of a new nucleus of research - translational neuroimaging in intellectual disability - with the initial objective of studying the aging process in DS by positron emission tomography (PET) imaging using specific radiopharmaceuticals for evaluation of neuroinflammation, deposition of beta-amyloid plaques and alterations in white matter, which are known to be altered in postmortem tissue analysis but not yet evaluated longitudinally by in vivo imaging. The study of these parameters will be done in a temporal and translational way, that is, evaluating, longitudinally, the changes throughout the life of DS animal model, and also in different age groups in DS people, as a proof-of-concept study. The characterization of changes in the profile of these processes, as well as the correlation between them, may lead to the identification of critical moments for initiation and therapeutic follow-up, or even development of new therapeutic interventions. (AU)

Scientific publications

(7)

(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)

BUSATTO, GERALDO F.; DE GOBBI PORTO, FABIO HENRIQUE; FARIA, DANIELE DE PAULA; SQUARZONI, PAULA; COUTINHO, ARTUR MARTINS; GARCEZ, ALEXANDRE TELES; PENTEADO ROSA, PEDRO GOMES; DA COSTA, NAOMI ANTUNES; CARVALHO, CLEUDIANA LIMA; TORRALBO, LETICIA; et al. In vivo imaging evidence of poor cognitive resilience to Alzheimer's disease pathology in subjects with very low cognitive reserve from a low-middle income environment. ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING, v. 12, n. 1, 2020. (18/15167-1, 14/50873-3)

BUSATTO FILHO, GERALDO; DURAN, FABIO LUIZ DE SOUZA; SQUARZONI, PAULA; COUTINHO, ARTUR MARTINS NOVAES; ROSA, PEDRO GOMES PENTEADO; TORRALBO, LETICIA; PACHI, CLARICE GAMEIRO DA FONSECA; DA COSTA, NAOMI ANTUNES; PORTO, FABIO HENRIQUE DE GOBBI; CARVALHO, CLEUDIANA LIMA; et al. Hippocampal subregional volume changes in elders classified using positron emission tomography-based Alzheimer's biomarkers of beta-amyloid deposition and neurodegeneration. Journal of Neuroscience Research, v. 99, n. 2, p. 481-501, FEB 2021. (18/15167-1)

PITOMBEIRA, MILENA SALES; KOOLE, MICHEL; CAMPANHOLO, KENIA R.; SOUZA, ALINE M.; DURAN, FABIO L. S.; FONTOURA SOLLA, DAVI J.; MENDES, MARIA F.; APOSTOLOS PEREIRA, SAMIRA L.; RIMKUS, CAROLINA M.; BUSATTO, GERALDO FILHO; et al. Innate immune cells and myelin profile in multiple sclerosis: a multi-tracer PET/MR study. EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, v. 49, n. 13, p. 16-pg., 2022-07-15. (18/15167-1)

CAMPANHOLO, K. R.; PITOMBEIRA, M. S.; RIMKUS, C. M.; MENDES, M. F.; APOSTOLOS-PEREIRA, S. L.; BUSATTO FILHO, G.; CALLEGARO, D.; BUCHPIGUEL, C. A.; DURAN, F. L. S.; DE PAULA FARIA, D.. Myelin imaging measures as predictors of cognitive impairment in MS patients: A hybrid PET-MRI study. MULTIPLE SCLEROSIS AND RELATED DISORDERS, v. 57, p. 9-pg., 2022-01-01. (18/15167-1)

WIAZOWSKI SPELTA, LIDIA EMMANUELA; REAL, CAROLINE CRISTIANO; BUCHPIGUEL, CARLOS ALBERTO; FARIA, DANIELE DE PAULA; MARCOURAKIS, TANIA. [F-18]FDG brain uptake of C57Bl/6 male mice is affected by locomotor activity after cocaine use: A small animal positron emission tomography study. Journal of Neuroscience Research, v. N/A, p. 14-pg., 2022-07-02. (18/15167-1)

DE OLIVEIRA, LAURA CAVALCANTI; DE PAULA FARIA, DANIELE. Pharmacological Approaches to the Treatment of Dementia in Down Syndrome: A Systematic Review of Randomized Clinical Studies. Molecules, v. 27, n. 10, p. 11-pg., 2022-05-01. (18/15167-1, 20/11728-9)

FARIA, DANIELE DE PAULA; REAL, CAROLINE CRISTIANO; DE SOUZA, LARISSA ESTESSI; GARCEZ, ALEXANDRE TELES; NAVARRO MARQUES, FABIO LUIS; BUCHPIGUEL, CARLOS ALBERTO. Positron Emission Tomography Imaging for In Vivo Measuring of Myelin Content in the Lysolecithin Rat Model of Multiple Sclerosis. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, v. N/A, n. 168, p. 12-pg., 2021-02-01. (18/15167-1, 19/15654-2)