Expression Profiling of Cytokine, Cholinergic Markers, and Amyloid-beta Deposition in the APP(SWE)/PS1dE9 Mouse Model of Alzheimer's Disease Pathology

作者:Reale Marcella*; D'Angelo Chiara; Costantini Erica; Di Nicola Marta; Yarla Nagnedra Sastry; Kamal Mohammad Amjad*; Salvador Nieves; Perry George
来源:Journal of Alzheimer's Disease, 2018, 62(1): 467-476.
DOI:10.3233/JAD-170999

摘要

Background: Alzheimer's disease (AD), a neurodegenerative disease, is associated with dysfunction of the olfactory and the entorhinal cortex of the brain that control memory and cognitive functions and other daily activities. Pro-inflammatory cytokines, amyloid-beta (A beta), and the cholinergic system play vital roles in the pathophysiology of AD. However, the role of changes in cholinergic system components, A beta accumulation, and cytokines in both the olfactory and entorhinal cortex is not known clearly.
Objective: The present study is aimed to evaluate the changes of cholinergic system components, A beta accumulation, and cytokines in both the olfactory bulb (OB) and entorhinal cortex (EC) of young and aged APP(SWE)/PS1dE9 transgenic (Tg) mice.
Methods: We have explored the changes of cholinergic system components, A beta accumulation, and expression profiling of cytokines in the OB and EC of aged APPswe transgenic mice and age-matched wild type mice using quantitative Real-Time PCR assays and immunohistochemistry techniques.
Results: In aged Tg mice, a significant increase of expression of interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, and chemokine MCP1 (p < 0.001, p < 0.001, and p = 0.001, respectively) and a significant reduction of nAChR alpha 4 (p = 0.048) and AChE (p = 0.023) was observed when compared with age-matched wild type mice. Higher levels of AChE and BuChE are expressed in OB and EC of the APPSWE/PS1dE9 of Tg mice. A beta accumulation was observed in OB and EC of the APP(SWE)/PS1dE9 of Tg mice.
Conclusion: The study demonstrates the expression profiling of pro-inflammatory cytokines and cholinergic markers as well as A beta accumulation in OB and EC of the APP(SWE)/PS1dE9 Tg mice. Moreover, the study also demonstrated that the APP(SWE)/PS1dE9 Tg mice can be useful as a mouse model to understand the role of pro-inflammatory cytokines and cholinergic markers in pathophysiology of AD.

  • 出版日期2018