BACE1 Glycosylation as a Potential Biomarker for Early Alzheimer's Disease Diagnosis

• Grant number: 25/09770-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: October 01, 2025
• End date: September 30, 2026
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
• Principal Investigator: Emanuel Carrilho
• Grantee: Letícia Gaiola
• Supervisor: Andras Guttman
• Host Institution: Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Institution abroad: University Of Debrecen, Hungary
• Associated to the scholarship: 24/03238-2 - Peptide mapping for analysis of PTMs of innovative reference mAbs for Alzheimer's Disease and biosimilars by CE-MS: verification of the potential of the least expensive drug for therapy., BP.DD

Abstract

Alzheimer's disease (AD) is the most common cause of dementia worldwide and remainsdifficult to diagnose in its early stages. Current methods, including neuroimaging and fluidbiomarkers, are often invasive, expensive, or insufficiently sensitive. Recent studies have shownthat aberrant protein glycosylation-particularly the presence of bisecting N-acetylglucosamine(GlcNAc)-is involved in AD pathogenesis and may precede clinical onset. BACE1, the enzymeinitiating ¿-amyloid (A¿) production, is regulated by N-glycosylation, which affects its stabilityand activity. This project will investigate the glycosylation profile of BACE1, focusing on bisectingGlcNAc, to assess its potential as an early and specific biomarker for AD. Samples from ADpatients, individuals with other dementias, and healthy controls will be analyzed using capillaryelectrophoresis combined with mass spectrometry (CE-ESI-MS), laser-induced fluorescencedetection (CE-LIF), and SDS capillary gel electrophoresis (SDS-CGE). The association betweenBACE1 glycosylation patterns and clinical data may enable the development of a sensitive,minimally invasive diagnostic approach. This study also aims to strengthen Brazilian expertise inbiomarker discovery and biopharmaceutical analysis, while promoting internationalcollaboration in the search for more accurate and accessible tools for early AD diagnosis.