Neuron-specific cellular functions of Interleukin-9 in Alzheimer’s Disease Open Access

Abstract

The deposition of beta-amyloid and tau initiate immune responses in the brain that lead to neuroinflammation in Alzheimer’s Disease (AD). Increased rates of pro-inflammatory and anti-inflammatory cytokines such as Interleukin-9 (IL-9) are observed in AD. Previously, our lab found African Americans with AD had a higher increase in Cerebrospinal Fluid (CSF) IL- 9 levels than those with Normal Cognition (NC), but this was not true for Caucasians. Using immunohistochemical analysis for brain IL-9, we found greater brain IL-9 levels also associated with AD in African Americans but not Caucasians. The direct mechanism by which IL-9 acts on brain specific neurons remains to be elucidated. Here, we aimed at studying the role of IL-9 in the transmission and modulation of neuronal signals in the brain by investigating differential IL-9 and IL-9 Receptors (IL-9R) expression in cases with and without AD. Using postmortem brain slides from older African Americans and Caucasians, we utilized an immunohistochemical staining method to stain for IL-9R. We also aimed to observe the differences in density of the IL-9 receptor with or without ongoing cell loss. For the first time, we successfully identified the presence of IL-9R on neuronal cells, localizing around the cell body. We also found an upregulation of IL-9R in AD in comparison to control cases, and increased levels of perivascular IL-9 in comparison to parenchymal IL-9 in Caucasian AD cases which was not true for African American AD cases. These results support the finding that IL-9 has AD specific effects on the brain, and may be a key cytokine leading to the observed racial differences in AD. 

Table of Contents

Introduction 1

Materials & Methods 5

Results 8

Discussions 12

References 14 

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Neuroscience Health Sciences, Aging Health Sciences, Immunology
Keyword	Interleukin-9 Neuroinflammation Alzheimer's Disease Aging
Committee Chair / Thesis Advisor	William Hu, Emory University
Committee Members	Sara Culpepper, Emory University Rachelle Spell, Emory University Nicole Gerardo, Emory University

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