Basic Science and Pathogenesis

Area of Science:

• Neuroscience
• Biochemistry
• Analytical Chemistry

Background:

• Alzheimer's disease (AD) is a progressive neurodegenerative disorder with distinct metabolic changes.
• Vulnerable neocortical areas like DLPFC are affected early, while resilient areas like V1 are affected later.
• Spatial characterization of molecular changes is crucial for understanding AD progression.

Purpose of the Study:

• To optimize Desorption Electrospray Ionization Mass Spectrometry Imaging (DESI-MSI) methods for analyzing brain tissues.
• To spatially characterize Alzheimer's disease-related molecular changes in dorsolateral prefrontal cortex (DLPFC) and primary visual cortex (V1).
• To compare metabolite and lipid signatures between formalin-fixed paraffin-embedded (TMA FFPE) and fresh frozen brain tissues.

Main Methods:

• Postmortem DLPFC (healthy, frozen) and V1 (AD, TMA FFPE) brain tissues were analyzed using DESI-MSI.
• TMA FFPE tissues underwent deparaffinization and ammonium treatment before MSI analysis.
• Experiments focused on optimizing methods and comparing molecular recovery between tissue formats.

Main Results:

• DESI-MSI detected 97 metabolites in frozen DLPFC and 29 in TMA FFPE V1 in negative mode.
• Specific metabolites like pyruvic acid and lactic acid were detected in both formats.
• Frozen tissues showed higher overall metabolite recovery compared to TMA FFPE tissues.

Conclusions:

• TMA FFPE tissues are a viable, though limited, alternative to frozen tissues for spatial molecular mapping in AD.
• FFPE tissues are more accessible and compatible with histological techniques.
• Spatial MSI is a valuable tool for broad molecular analysis across brain regions in AD, aiding biomarker discovery.