Effect of cholinesterase inhibitor on APP metabolism in platelets

• Grant number: 13/20695-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: February 01, 2014
• End date: September 30, 2015
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Agreement: STIC-AmSud
• Principal Investigator: Orestes Vicente Forlenza
• Grantee: Tamires Alves Sarno
• Host Institution: Instituto de Psiquiatria Doutor Antonio Carlos Pacheco e Silva (IPq). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Alzheimer's disease (AD) is characterized by a progressive neurodegeneration of the central nervous system (CNS). It is the most common cause of dementia and can contribute to 60-70% of the cases. It is a condition marked by a pathological triad, characterized by accumulation of extracellular aggregates of amyloid beta protein (Aß), originated from proteolytic processes of amyloid precursor protein (APP) that cause senile plaques, intracellular tangles of hyperphosphorylated tau and neuronal loss. Currently the diagnosis of AD is based on the DSM (Diagnostic and Statistical Manual of Mental Disorders - Diagnostic and Statistical Manual of Disorders), however, the final diagnosis can only be made post mortem by brain biopsy. Under normal physiological conditions, the proteolytic processing of APP occurs via non-amyloidogenic by the action of the enzimes ± (ADAM10) and g secretase. Under pathological conditions, APP is cleaved by the amyloidogenic pathway, producing the toxic fragments of Ab42, by the action of ² secretase (BACE1). The platelets have been used as a model of peripheral diagnosis, allowing its use as a peripheral marker of brain metabolism, by reflecting certain physiological processes in the central nervous system. Most of the circulating APP (95%) is present in platelets. Platelets have all enzymatic machinery to produce the fragments of APP via beta secretase (BACE1), alpha secretase (ADAM10) and gamma-secretase. The objective of this study is to verify the effect of donepezil (cholinesterase inhibitor) under APP metabolism. To do so a longitudinal study of 6 months is planned, in which we will evaluate the ratio of APP and the enzimes BACE1, ADAM10 and gamma-secretase in AD patients before starting the medication, 3 and 6 months later. (AU)

Scientific publications

(4)

(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)

BRAM, JESSYKA MARIA DE FRANCA; TALIB, LEDA LEME; JOAQUIM, HELENA PASSARELLI GIROUD; SARNO, TAMIRES ALVES; GATTAZ, WAGNER FARID; FORLENZA, ORESTES VICENTE. Protein levels of ADAM10, BACE1, and PSEN1 in platelets and leukocytes of Alzheimer's disease patients. EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, v. 269, n. 8, p. 963-972, DEC 2019. (13/20695-3, 09/52825-8)

SARNO, TAMIRES ALVES; TALIB, LEDA LEME; GIROUD JOAQUIM, HELENA PASSARELLI; DE FRANCA BRAM, JESSYKA MARIA; GATTAZ, WAGNER FARID; FORLENZA, ORESTES VICENTE. Protein Expression of BACE1 is Downregulated by Donepezil in Alzheimer's Disease Platelets. JOURNAL OF ALZHEIMER'S DISEASE, v. 55, n. 4, p. 1445-1451, 2017. (13/20695-3, 09/52825-8)

RADANOVIC, MARCIA; FACCO, GIULIANA; FORLENZA, ORESTES V.. Sensitivity and specificity of a briefer version of the Cambridge Cognitive Examination (CAMCog-Short) in the detection of cognitive decline in the elderly: An exploratory study. INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, v. 33, n. 5, p. 769-778, MAY 2018. (09/52825-8, 13/20695-3)

DE-PAULA, VANESSA DE J. R.; FORLENZA, ANDREA S.; FORLENZA, ORESTES V.. Relevance of gutmicrobiota in cognition, behaviour and Alzheimer's disease. PHARMACOLOGICAL RESEARCH, v. 136, p. 29-34, OCT 2018. (16/01302-9, 13/20695-3, 09/52825-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SARNO, Tamires Alves. Effect of Acetylcholinesterase inhibitors on amyloid precursor protein metabolism in platelets. 2016. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.