Association between LDL cholesterol levels and ADAM10 in carriers and non-carriers of the APOE e4 allele

• Grant number: 24/03123-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2024
• End date: May 31, 2025
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Márcia Regina Cominetti
• Grantee: Mateus Balleiro Bertoldo Garcia
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated research grant: 21/01863-9 - Biology and function of ADAM10 isoforms for differential diagnosis of Alzheimer's Disease by electrochemical sensors, AP.TEM

Abstract

Alzheimer's disease (AD) is the most prevalent form of dementia, characterized by a multifactorial and irreversible neurodegenerative process. At the microscopic level, there is an abnormal accumulation of beta-amyloid peptide (bA), which aggregates in extracellular senile plaques, and hyperphosphorylation of tau protein, resulting in intracellular neurofibrillary tangles. Disintegrin and metalloprotease 10 (ADAM10) is a protein present in neurons, platelets, cerebrospinal fluid (CSF), and leukocytes, and is capable of cleaving the amyloid precursor protein (APP), acting in the non-amyloidogenic pathway and thus preventing the formation of bA. Our group found increased levels of the inactive isoform of this protein in the plasma and CSF of people with AD compared to the levels of cognitively healthy people. These studies made it possible to classify ADAM10 as a candidate peripheral biomarker for AD. Peripheral biomarkers are cheaper and less invasive than current diagnostic tests for the disease and promise to revolutionize clinical practice worldwide. Low-density lipoproteins (LDL) are responsible for transporting cholesterol throughout the body. However, excess LDL can accumulate in the arteries, increasing the risk of developing cardiovascular diseases, such as atherosclerosis. Therefore, investigating a possible association between LDL and ADAM10 levels in cognitively healthy people carrying the Apolipoprotein E (APOE) e4 polymorphism will help better understand the disease and provide relevant information for future prevention and treatment strategies. Therefore, this project aims to analyze whether increased LDL levels are associated with ADAM10 levels in healthy older adults carrying the APOE e4 polymorphism.