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Basic Science and Pathogenesis.

Tassia Venga Mendes1, Patrick R Hof2, Daniel Meyer3

  • 1Baylor College of Medicine, Houston, TX, USA.

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|December 24, 2025
PubMed
Summary
This summary is machine-generated.

Desorption Electrospray Ionization Mass Spectrometry Imaging (DESI-MSI) successfully mapped Alzheimer's disease (AD) molecular changes in brain tissues. While frozen samples offered higher metabolite recovery, formalin-fixed paraffin-embedded (TMA FFPE) tissues are viable for spatial analysis in AD research.

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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.