PLASMATIC PHOSPHATIDYLCHOLINE AS A BIOMARKERS FOR ALZHEIMER'S DEMENTIA IN INDIVIDUALS WITH DOWN SYNDROME

• Grant number: 25/01695-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2025
• End date: May 31, 2026
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Leda Leme Talib
• Grantee: Bruna Berribilli Bortoleto
• 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

As the life expectancy of individuals with Down Syndrome (DS) increases, they exhibit dementia-related aging associated with the development of Alzheimer's Disease (AD), partly because the amyloid precursor protein (APP), which plays a crucial role in AD pathogenesis, is located on chromosome 21-the same chromosome affected by trisomy in DS. Consequently, the overexpression of the APP gene in individuals with DS leads to the formation of beta-amyloid plaques in the central nervous system, a hallmark of AD. Furthermore, recent studies conducted by our group and others suggest abnormalities in the lipidomic profile of AD patients, particularly in the analysis of lipid metabolites in plasma. However, studies on the plasma lipid profile of DS patients are still lacking in the literature. Therefore, considering the pathophysiological relationship between DS and AD, the present study aims to evaluate the potential of phosphatidylcholine as a biomarker for DS. Two experimental groups will be considered: (1) individuals with cognitive decline due to AD and (2) DS individuals with cognitive impairment. Control groups will consist of healthy young and elderly individuals. High-Pressure Liquid Chromatography coupled with Mass Spectrometry (HPLC-MS/MS) will be used for lipidomic analysis. Our main hypothesis is that plasmatic phosphatidylcholine levels in DS patients can serve as a biomarker for AD development and, moreover, that this metabolite may have prognostic value for AD progression.