Gabriel Trigo Pereira

Characterization of Plasma and CSF Glycoproteomic Signatures Associated with Cognitive Decline and Modifiable Risk Factors

Can changes in protein glycosylation help us better understand cognitive decline and its underlying molecular mechanisms?

Dementia encompasses several conditions characterized by progressive cognitive impairment. Although considerable progress has been made in identifying disease-associated proteins and genetic risk factors, many molecular mechanisms underlying cognitive decline remain incompletely understood. In particular, protein glycosylation represents an important but still relatively unexplored layer of molecular information. Gabriel's research investigates the proteomic and glycoproteomic profiles of blood plasma and cerebrospinal fluid (CSF) from participants in the Brazilian BioAz cohort, a longitudinal study involving older adults with memory complaints. By integrating information on protein abundance and glycosylation with clinical assessments and modifiable risk factors, such as metabolic and lifestyle-related conditions, the project aims to identify molecular patterns associated with cognitive decline.

Research Approach

A central objective of Gabriel's research period at the University of Groningen is the development and optimization of a sensitive and reproducible LC-MS-based glycoproteomics workflow.

This includes:

• Sample preparation: Optimizing workflows for complex biological fluids, including strategies to reduce interference from highly abundant plasma proteins.

• Glycopeptide enrichment: Developing methods to improve the detection of low-abundance glycosylated peptides.

• LC-MS/MS analysis: Applying high-resolution mass spectrometry to characterize glycoproteins and their glycosylation patterns.

• Data interpretation: Establishing computational approaches for the identification and comparison of glycopeptides across biological samples.

• Multi-omics integration: Combining glycoproteomics with global proteomics, clinical information, and other molecular datasets.

The optimized methods will subsequently support investigations of the BioAz cohort in Brazil.

Scientific Relevance

By extending conventional proteomics towards the characterization of protein glycosylation, this research aims to reveal molecular information that cannot be captured from protein abundance measurements alone. Ultimately, the project seeks to contribute to a more comprehensive understanding of the biological pathways associated with cognitive impairment and the influence of modifiable dementia risk factors.