Effects of Low Density Lipoprotein (LDL) Treatment on ADAM10 Expression in Neuronal and Endothelial Cells: A Molecular Investigation of Modifiable Risk Factors for Dementia

• Grant number: 24/05940-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2024
• End date: August 31, 2026
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Márcia Regina Cominetti
• Grantee: Ana Beatriz Aparecida Targas
• 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 neurodegenerative, gradual, and progressive, characterized by cortical atrophy predominant in the medial temporal lobe, extensive neuronal losses, deposits of neurofibrillary tangles, and amyloid plaques. An intermediate stage between normal cognition and AD is mild cognitive impairment (MCI), which can be reversed. Knowledge about the pathophysiology of AD has presented different molecular biomarkers, such as ADAM10, the main neuronal ±-secretase, also present in platelets, leukocytes, and cerebrospinal fluid (CSF). This protein is capable of acting in the non-amyloidogenic pathway of amyloid precursor protein (APP) cleavage and, therefore, prevents the formation of amyloid-² peptide (A²), one of the pathological hallmarks of AD. Thus, assessment of ADAM10 levels in the plasma of patients suspected of having cognitive decline but who have not yet achieved such decline may allow for early interventions that could delay or prevent AD. Considering that this disease has several modifiable risk factors, such as obesity, hypertension, and diabetes, the objectives of the present project will be to evaluate the effects of treating endothelial cells (HMEC-1), neuron-like cells (differentiated SH-SY5Y), and astrocytes like-cell with (CCF-STTG1) lipoproteins of low-density (LDL) on ADAM10 gene and protein expression using RT-qPCR and western blotting techniques. The expected results will be a lower expression of ADAM10 after the treatment of cells with LDL, which could help to understand the effects of factors such as obesity, hypertension, and diabetes on the development and progress of dementia.