Reversal of Paralysis and Reduced Inflammation from Peripheral Administration of β-Amyloid in TH1 and TH17 Versions of Experimental Autoimmune Encephalomyelitis

beta-Amyloid 42 (A beta 42) and beta-amyloid 40 (A beta 40), major components of senile plaque deposits in Alzheimer's disease, are considered neurotoxic and proinflammatory. In multiple sclerosis, A beta 42 is up-regulated in brain lesions and damaged axons. 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 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 A beta 42 and A beta 40 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 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 wild-type 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. Because 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.