Objective:

To analyze age- and disease-related changes in brain proteins and sugar molecules using a spatial mass spectrometry workflow.

Key Findings:

• Identified over 4,000 proteins, two to three times more than previous methods.
• Increased abundance of synapse-related proteins in aged mouse brains indicating age-associated synaptic remodeling.
• Altered extracellular matrix proteins and reduced chondroitin sulfate glycans in human tissue with Alzheimer’s disease and Lewy body pathology.

Interpretation:

The findings highlight significant molecular changes associated with aging and neurodegeneration, emphasizing the importance of glycosylation and extracellular matrix remodeling in these processes.

Limitations:

• The study primarily focused on specific brain regions and may not represent the entire brain's molecular landscape.
• Further validation in larger cohorts is needed to confirm findings.

Conclusion:

The developed workflow offers a high-resolution method for spatially resolved glycomic and proteomic profiling, potentially aiding in biomarker discovery and improving diagnosis and treatment of neurodegenerative diseases.