Examining an unexpected protective role of amyloid-beta in experimental autoimmune encephalomyelitis
Abstract/Contents
- Abstract
- [Beta]-amyloid-42 (A[beta]42) and [beta]-amyloid-40 (A[beta]40), major components of senile plaque deposits in Alzheimer's disease (AD), are considered neurotoxic and pro-inflammatory. In Multiple Sclerosis (MS), A[beta]42 is upregulated in brain lesions and damaged axons. Here we found, unexpectedly, that treatment with either A[beta]42 or A[beta]40 peptides reduced motor paralysis and brain inflammation in four different models of experimental autoimmune encephalomyelitis (EAE) with attenuation of motor paralysis, reduction of inflammatory lesions in the central nervous system (CNS), and suppression of lymphocyte activation. A[beta]42 and A[beta]40 treatments were effective in reducing ongoing paralysis induced with adoptive transfer of either autoreactive Th1 or Th17 cells. High-dimensional 14-parameter flow cytometry of peripheral immune cell populations after in vivo A[beta]2 and A[beta]40 treatment revealed substantial modulations in the percentage of lymphoid and myeloid subsets during EAE. Major pro-inflammatory cytokines and chemokines were reduced in the blood following A[beta] peptide treatment. Protection conferred by A[beta] treatment did not require its delivery to the brain: adoptive transfer with lymphocytes from donors treated with A[beta]42 attenuated EAE in WT recipient mice and A[beta] deposition in the brain was not detected in treated EAE mice by immunohistochemical analysis. In contrast to the improvement in EAE with A[beta]-treatment, EAE was worse in mice with genetic deletion of the amyloid precursor protein. Therefore, in the absence of A[beta] there is exacerbated clinical EAE disease progression. Since A[beta]42 and A[beta]40 ameliorate experimental autoimmune inflammation targeting the CNS, we might now consider its potential anti-inflammatory role in other neuropathological conditions.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2012 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Grant, Jacqueline Leigh, Ms | |
|---|---|---|
| Associated with | Stanford University, Department of Neurology. | |
| Primary advisor | Steinman, Lawrence | |
| Thesis advisor | Steinman, Lawrence | |
| Thesis advisor | Han, May Htwe | |
| Thesis advisor | Utz, Paul | |
| Thesis advisor | Wyss-Coray, Anton | |
| Advisor | Han, May Htwe | |
| Advisor | Utz, Paul | |
| Advisor | Wyss-Coray, Anton |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Jacqueline Leigh Grant. |
|---|---|
| Note | Submitted to the Department of Neurology. |
| Thesis | Ph.D. Stanford University 2012 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2012 by Jacqueline Leigh Grant
- License
- This work is licensed under a Creative Commons Attribution 3.0 Unported license (CC BY).
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