Age & the Inflammatory Microenvironment in APP/PS1 Mice

Table of Contents

Abstract

Presentation

01. Introduction 02. Neuroinflammation Classification 03. Microglial Activation 04. Plaque Microenvironment 05. AD Mouse Model 06. Age & Amyloid 07. Age & Neuroinflammation 08. Age & Microglial Activation 09. Microenvironment Analysis 10. Age & Inflammatory Microenvironment 11. Summary

https://opt003stagmediafiles.blob.core.windows.net/image/63269c1e1b2c4d7eb5a3bd3f04f7a571

Age-dependent changes in activated microglia density (A) and GFAP stain density (B) inside amyloid plaques ("local") in the cerebral cortex of ARTE10 mice compared to levels not associated with plaques ("global") in wild-type mice. N=10-12 per group. Statistical analysis was performed using Kruskal-Wallis non-parametric test and Dunn’s multiple comparisons test. *p<0.05; **p<0.005; ***p<0.001; ****p<0.0001.

https://opt003stagmediafiles.blob.core.windows.net/image/4b522aabe87c4f38a26663a3da8b21f0

Age-dependent changes in activated microglia density (A) and GFAP stain density (B) not locally associated with amyloid plaques in the cerebral cortex of ARTE10 and WT mice. N=10-12 per group. Statistical analysis was performed using Kruskal-Wallis non-parametric test and Dunn’s multiple comparisons test. *p<0.05; **p<0.005; ***p<0.001; ****p<0.0001.

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If we restrict the analysis to quantify the inflammation inside the plaque core and compare it to inflammation levels outside of the plaques, we observe a significant difference between the global levels in wild-type mice and the plaque core levels as early as 6 months in transgenic mice, both for activated microglia density and GFAP stain density.

This significant difference was not observable when solely comparing global levels for the same metrics at 6 months. Interestingly, the core levels of GFAP and activated microglia density do not appear to change significantly as the animals get older as indicated in the top figure.

On the other hand, we can still observe a time-dependent increase in neuroinflammation outside the plaque, as indicated in the bottom figure, suggesting that the majority of the observable microgliosis and astrogliosis in early pathology is located in close proximity to plaques and tends to increase further away from plaques as the pathology progresses.