LMD proteomics provides evidence for hippocampus field-specific motor protein abundance changes with relevance to Alzheimer's disease

- Laser microdissection-proteomics was used for hippocampal field analytics.
- Prominent motor protein changes were identified between CA1, CA2, and CA3.
- Motor proteins revealed AD-specific depletion in CA1 vs. CA2, CA3.
- Findings suggest specific vulnerability of CA1 for transport-associated proteins.

BackgroundHuman hippocampal area Cornu Ammonis (CA) 1 is one of the first fields in the human telencephalon showing Alzheimer disease (AD)-specific neuropathological changes. In contrast, CA2 and CA3 are far later affected pointing to functional differences, which may be accompanied by differences in proteome endowment and changes.MethodsHuman pyramidal cell layers of hippocampal areas CA1, CA2, and CA3 from neurologically unaffected individuals were excised using laser microdissection. The proteome of each individual sample was analyzed and differentially abundant proteins were validated by immuno-histochemistry.ResultsComparison of CA1 to CA2 revealed 223, CA1 to CA3 197 proteins with differential abundance, among them we found motor proteins MYO5A and DYNC1H1. Extension of the study to human hippocampus slices from AD patients revealed extensive depletion of these proteins in CA1 area compared to unaffected controls.ConclusionHigh abundance of motor proteins in pyramidal cell layers CA1 compared to CA2 and CA3 points the specific vulnerability of this hippocampal area to transport-associated changes based on microtubule dysfunction and destabilization in AD.