A-T.46: Spatial Cell-Cell Communication in Alzheimer's Disease
Amyloid precursor protein (APP) is a transmembrane protein expressed in neurons and is involved in synapse formation and cell signaling. In the amyloidogenic pathway associated with Alzheimer's disease, APP contributes to the generation of amyloid-β peptides, which aggregate into plaques, disrupt synaptic function, activate astrocytes, and induce metabolic dysfunction.
In Alzheimer's disease, astrocytes responsible for Aβ clearance become reactive, reducing their clearance capacity and transitioning to a pro-inflammatory phenotype. Epoxyeicosatrienoic acids (EETs) counteract this reactivity, but their degradation by soluble epoxide hydrolase (sEH), which is upregulated near plaques, limits this effect. Genetic deletion of sEH (sEH-KO) has been linked to reduced astrocyte reactivity and improved metabolic function.
We analyze 10x Genomics Visium spatial transcriptomics data from APPF1 mouse brain tissue, comparing sEH-KO and control conditions. Our focus is on spatial gene expression changes related to astrocyte signatures and metabolic pathways, assessing how sEH-KO alters astrocyte metabolism.
While sEH-KO has been studied in Alzheimer's pathology, less is known about how its effects are spatially organized within brain tissue. By applying spatially resolved analysis, we investigate the topological structure of cell-cell communication networks associated with astrocyte transcriptomic and metabolic shifts.
Our approach includes quality control, cell type deconvolution, and spatial clustering. We further explore cell-cell communication to identify ligand-receptor interactions between astrocyte and neighboring cell types to identify spatial communication patterns and localize functional hotspots within the brain.
Co-authors: Nina Baumgarten, Ingrid Fleming, Jasmin Hefendehl, Marcel H. Schulz
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