- Quantification of the astrocytic morphology is a sensitive metric of the disease state
- Astrocytes and microglia have different spatiotemporal relationships to amyloid-β plaques
- Microglia accumulate directly on or around the plaques, while astrocytes accumulate further away
- Microglia density increases progressively as a function of plaque size, and then plateaus
- The hypertrophic astrocytic density increases close to the plaque as the plaque size increase, but the density on the plaques decreases in larger plaques
- The microglia-to-astrocyte ratio is a sensitive metric of the later disease stages
In summary, we have seen how the fully-automated quantification of astrocyte morphology can provide a sensitive metric of the disease state. In our APP/PS1 mouse model, it showed changes with higher statistical significance. This result means that this metric would enable the detection of smaller effect size in preclinical therapeutic efficacy studies.
In addition, we quantified the plaque cellular microenvironment as a function of plaque size. This data showed very different behaviors for microglia and astrocytes. Microglia progressively accumulated on the plaques, while astrocytes showed a more global response. The density of hypertrophic astrocytes on the plaque increased from small to medium size plaques, and then decreased in larger plaques. We thus created a metric based on this differential behavior, the ratio of microglia to astrocyte on plaques, which provided a sensitive metric of the later disease stages.