Reversal of Paralysis and Reduced Inflammation from Peripheral Administration of beta-Amyloid in T(H)1 and T(H)17 Versions of Experimental Autoimmune Encephalomyelitis SCIENCE TRANSLATIONAL MEDICINE Grant, J. L., Ghosn, E. E., Axtell, R. C., Herges, K., Kuipers, H. F., Woodling, N. S., Andreasson, K., Herzenberg, L. A., Herzenberg, L. A., Steinman, L. 2012; 4 (145)

Abstract

ß-Amyloid 42 (Aß42) and ß-amyloid 40 (Aß40), major components of senile plaque deposits in Alzheimer's disease, are considered neurotoxic and proinflammatory. In multiple sclerosis, Aß42 is up-regulated in brain lesions and damaged axons. We found, unexpectedly, that treatment with either Aß42 or Aß40 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. Aß42 and Aß40 treatments were effective in reducing ongoing paralysis induced with adoptive transfer of either autoreactive T helper 1 (T(H)1) or T(H)17 cells. High-dimensional 14-parameter flow cytometry of peripheral immune cell populations after in vivo Aß42 and Aß40 treatment revealed substantial modulations in the percentage of lymphoid and myeloid subsets during EAE. Major proinflammatory cytokines and chemokines were reduced in the blood after Aß peptide treatment. Protection conferred by Aß treatment did not require its delivery to the brain: Adoptive transfer with lymphocytes from donors treated with Aß42 attenuated EAE in wild-type recipient mice, and Aß deposition in the brain was not detected in treated EAE mice by immunohistochemical analysis. In contrast to the improvement in EAE with Aß treatment, EAE was worse in mice with genetic deletion of the amyloid precursor protein. Therefore, in the absence of Aß, there is exacerbated clinical EAE disease progression. Because Aß42 and Aß40 ameliorate experimental autoimmune inflammation targeting the CNS, we might now consider its potential anti-inflammatory role in other neuropathological conditions.

View details for DOI 10.1126/scitranslmed.3004145

View details for Web of Science ID 000307159500004

View details for PubMedID 22855462