Evaluation of platelet ADAM10 in non-Alzheimer's dementias

• Grant number: 15/26084-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2016
• End date: July 31, 2020
• Field of knowledge: Health Sciences - Nursing
• Principal Investigator: Márcia Regina Cominetti
• Grantee: Patricia Regina Manzine Moralles
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated scholarship(s): 17/13224-5 - Study of the JNK1 pathway as a selective target for the treatment of cognitive metabolic disorder: ADAM10 protein analysis, BE.EP.PD

Abstract

Dementia is characterized by progressive and global loss of cognitive function to the point of interfering in social and occupational activities of the individual, with dementia of Alzheimer's disease (AD) as a major example. Dementia affects about 5% of the population over 65 and the number becomes more significant after 75 years. Studies suggest that ADAM10 platelet levels in patients with AD are reduced in comparison to healthy individuals, however there is no comparisons of the expression and activity of this protein in other dementias. By comparing such levels, it would be possible to point out if ADAM10 is a specific biomarker for AD, or would also be altered in other dementias. Thus, this study aims to evaluate the expression and activity of platelet ADAM10 in dementia on type non-Alzheimer's: frontotemporal, vascular, Lewy and Parkinson's disease. This is a multicenter study with collaboration of four groups: Cognitive and Behavioral Neurology UFSCar (ANEU-UFSCar), Department of Clinical Medicine - UFMG, Department of Psychiatry - USP and Department of Neuroscience and Behavioral Sciences - FMRP. Participants will be divided into groups according to the type of dementia. Neuropsychological tests for cognitive assessment will be applied in all subjects. This study starts from the hypothesis that the levels and activity of ADAM10 are not changed in other dementias, making ADAM10 a specific biomarker molecule for AD. Peripheral blood colletion followed by protein analysis by Western blotting and fluorescence measured by peptide-specific cleavage activity assays will be performed. The data will be entered into a database to perform descriptive statistical analysis, chi-square test of Pearson, Kruskal-Wallis test followed by post-hoc test and the Mann-Whitney test considering statistical significance level of 5 % (p <0.05). (AU)

Scientific publications

(13)

(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)

BUSQUETS, ORIOL; ETTCHETO, MIREN; CANO, AMANDA; MANZINE, PATRICIA R.; SANCHEZ-LOPEZ, ELENA; ESPINOSA-JIMENEZ, TRIANA; VERDAGUER, ESTER; DARIO CASTRO-TORRES, RUBEN; BEAS-ZARATE, CARLOS; SUREDA, FRANCESC X.; et al. Role of c-Jun N-Terminal Kinases (JNKs) in Epilepsy and Metabolic Cognitive Impairment. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 1, JAN 1 2020. (17/13224-5, 15/26084-1)

REGINA MANZINE, PATRICIA; ETTCHETO, MIREN; CANO, AMANDA; BUSQUETS, ORIOL; MARCELLO, ELENA; PELUCCHI, SILVIA; DI LUCA, MONICA; ENDRES, KRISTINA; OLLOQUEQUI, JORDI; CAMINS, ANTONI; et al. ADAM10 in Alzheimer's disease: Pharmacological modulation by natural compounds and its role as a peripheral marker. BIOMEDICINE & PHARMACOTHERAPY, v. 113, MAY 2019. (17/13224-5, 15/24940-8, 15/26084-1)

POOR, SAGHAR RABIEI; ETTCHETO, MIREN; CANO, AMANDA; SANCHEZ-LOPEZ, ELENA; MANZINE, PATRICIA REGINA; OLLOQUEQUI, JORDI; CAMINS, ANTONI; JAVAN, MOHAMMAD. Metformin a Potential Pharmacological Strategy in Late Onset Alzheimer's Disease Treatment. PHARMACEUTICALS, v. 14, n. 9, SEP 2021. (17/13224-5, 15/26084-1)

ETTCHETO, MIREN; SANCHEZ-LOPEZ, ELENA; CANO, AMANDA; CARRASCO, MARINA; HERRERA, KATHERINE; MANZINE, PATRICIA R.; ESPINOSA-JIMENEZ, TRIANA; BUSQUETS, ORIOL; VERDAGUER, ESTER; OLLOQUEQUI, JORDI; et al. Dexibuprofen ameliorates peripheral and central risk factors associated with Alzheimer's disease in metabolically stressed APPswe/PS1dE9 mice. CELL AND BIOSCIENCE, v. 11, n. 1, JUL 22 2021. (17/13224-5, 15/26084-1)

MANZINE, PATRICIA R.; VATANABE, IZABELA P.; PERON, RAFAELA; GRIGOLI, MARINA M.; PEDROSO, V, RENATA; NASCIMENTO, CARLA M. C.; COMINETTI, MARCIA R.. Blood-based Biomarkers of Alzheimer's Disease: The Long and Winding Road. CURRENT PHARMACEUTICAL DESIGN, v. 26, n. 12, p. 1300-1315, 2020. (16/06226-9, 15/26084-1, 19/02648-4, 17/18808-5, 18/05446-0)

DE OLIVEIRA, TASSIA R.; MANZINE, PATRICIA R.; COMINETTI, MARCIA R.; LEITE, OLDAIR D.; FARIA, RONALDO C.. Electrochemical magneto-immunoassay for detection of ADAM10 Alzheimer's biomarker using gold nanoparticles as label. Talanta, v. 266, p. 8-pg., 2024-01-01. (17/24053-7, 15/26084-1, 17/24839-0, 15/19890-1, 21/01863-9)

PEREIRA VATANABE, IZABELA; PERON, RAFAELA; MANTELLATTO GRIGOLI, MARINA; PELUCCHI, SILVIA; DE CESARE, GIULIA; MAGALHAES, THAMIRES; MANZINE, PATRICIA REGINA; FIGUEREDO BALTHAZAR, MARCIO LUIZ; DI LUCA, MONICA; MARCELLO, ELENA; et al. ADAM10 Plasma and CSF Levels Are Increased in Mild Alzheimer's Disease. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 5, MAR 2021. (19/02648-4, 16/06226-9, 15/26084-1)

DE OLIVEIRA, TASSIA R.; ERBERELI, CAMILA R.; MANZINE, PATRICIA R.; MAGALHAES, THAMIRES N. C.; BALTHAZAR, MARCIO L. F.; COMINETTI, MARCIA R.; FARIA, RONALDO C.. Early Diagnosis of Alzheimer's Disease in Blood Using a Disposable Electrochemical Microfluidic Platform. ACS SENSORS, v. 5, n. 4, p. 1010-1019, APR 24 2020. (14/22401-0, 15/26084-1, 18/15571-7, 17/24839-0, 17/24053-7, 15/19890-1)

BUSQUETS, ORIOL; ERITJA, AURIA; LOPEZ, BLANCA M.; ETTCHETO, MIREN; MANZINE, PATRICIA R.; CASTRO-TORRES, RUBEN D.; VERDAGUER, ESTER; OLLEQUEQUI, JORDI; VAZQUEZ-CARRERA, MANUEL; AULADELL, CARME; et al. Role of brain c-Jun N-terminal kinase 2 in the control of the insulin receptor and its relationship with cognitive performance in a high-fat diet pre-clinical model. Journal of Neurochemistry, v. 149, n. 2, p. 255-268, APR 2019. (17/13224-5, 15/26084-1)

FOLCH, JAUME; ETTCHETO, MIREN; BUSQUETS, ORIOL; SANCHEZ-LOPEZ, ELENA; CASTRO-TORRES, RUBEN D.; VERDAGUER, ESTER; MANZINE, PATRICIA R.; RABIEI POOR, SAGHAR; LUISA GARCIA, MARIA; OLLOQUEQUI, JORDI; et al. The Implication of the Brain Insulin Receptor in Late Onset Alzheimer's Disease Dementia. PHARMACEUTICALS, v. 11, n. 1, MAR 2018. (17/13224-5, 15/26084-1)

PERON, RAFAELA; VATANABE, IZABELA PEREIRA; REGINA MANZINE, PATRICIA; CAMINS, ANTONI; COMINETTI, MARCIA REGINA. Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer's Disease Treatment. PHARMACEUTICALS, v. 11, n. 1, MAR 2018. (16/06226-9, 17/13224-5, 15/26084-1)

ETTCHETO, MIREN; OLLOQUEQUI, JORDI; SANCHEZ-LOPEZ, ELENA; BUSQUETS, ORIOL; CANO, AMANDA; REGINA MANZINE, PATRICIA; BEAS-ZARATE, CARLOS; CASTRO-TORRES, RUBEN D.; LUISA GARCIA, MARIA; BULLO, MONICA; et al. Benzodiazepines and Related Drugs as a Risk Factor in Alzheimer's Disease Dementia. FRONTIERS IN AGING NEUROSCIENCE, v. 11, JAN 8 2020. (17/13224-5, 15/26084-1)

ETTCHETO, MIREN; BUSQUETS, ORIOL; SANCHEZ-LOPEZ, ELENA; CANO, AMANDA; MANZINE, PATRICIA R.; VERDAGUER, ESTER; OLLOQUEQUI, JORDI; AULADELL, CARME; FOLCH, JAUME; CAMINS, ANTONI. The preclinical discovery and development of opicapone for the treatment of Parkinson's disease. EXPERT OPINION ON DRUG DISCOVERY, v. 15, n. 9, MAY 2020. (17/13224-5, 15/26084-1)