Aβ Microenvironment Analysis for Preclinical Drug Studies

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

By using a novel, robust, fully-automated approach, we have shown:

We can measure the density of neuroinflammatory cells, including activated microglia, as function of distance to β-amyloid plaques.
Our microenvironment analysis demonstrated:
- A very high level of activated microglia intimately associated with the plaques
- Age-dependent increase in neuroinflammation outside of the local plaque neighborhood

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This approach may provide sensitive measures for the preclinical assessment of the efficacy of putative disease-modifying therapeutic agents in this mouse model of Alzheimer's disease.

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In summary, our new approach allows for accurate, high throughput, and robust quantification of neuroinflammation in a β-amyloid mouse model of Alzheimer's disease. This method can distinguish between neuroinflammation that occurs in close proximity to β-amyloid plaques and global neuroinflammation that is distributed more distantly from plaques.

By adding this new spatial component to our tissue section analysis, we can potentially improve our characterization of the pathology and discover subtle effects that might not be readily apparent when looking only at the total level of neuroinflammation. This approach may provide sensitive measures for the evaluation of putative disease-modifying therapeutic agents for Alzheimer's disease.