Inflammatory Microenvironment Analysis in APP/PS1 Brains

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

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Examples of concentric radial ROIs derived from the β-amyloid plaque segmentation. The yellow contour lines illustrate the boundaries of the radial ROIs. All pixels on a given line are equidistant to the edge of a plaque. Scale bars are 10µm.

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Iba-1 stain density (A), microglia density (B), activated microglia density (C; inset shows full y-axis scale), and GFAP stain density (D) in the cerebral cortex of ARTE10 mouse model at 9 months-of-age as a function of the distance to plaques. The dashed lines indicate the levels of each metric in wild-type (WT) animals. 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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Analysis of the β-amyloid plaque microenvironment showed microgliosis primarily located less than 10µm away from the plaques, with higher Iba-1 stain density, total microglia, and activated microglia density compared to wild-type (WT) mice. Interestingly, the astrogliosis also showed an increase with proximity to the plaques, but was also increased outside of the local plaque microenvironment.

Of special note is the very high level of activated microglia at 0µm distance - see the inset in Panel C of the bottom figure.