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Reversal of paralysis and reduced inflammation from peripheral administration of ?-amyloid in TH1 and TH17 versions of experimental autoimmune encephalomyelitis.

ABSTRACT: ?-Amyloid 42 (A?42) and ?-amyloid 40 (A?40), major components of senile plaque deposits in Alzheimer's disease, are considered neurotoxic and proinflammatory. In multiple sclerosis, A?42 is up-regulated in brain lesions and damaged axons. We found, unexpectedly, that treatment with either A?42 or A?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?42 and A?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?42 and A?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? peptide treatment. Protection conferred by A? treatment did not require its delivery to the brain: Adoptive transfer with lymphocytes from donors treated with A?42 attenuated EAE in wild-type recipient mice, and A? deposition in the brain was not detected in treated EAE mice by immunohistochemical analysis. In contrast to the improvement in EAE with A? treatment, EAE was worse in mice with genetic deletion of the amyloid precursor protein. Therefore, in the absence of A?, there is exacerbated clinical EAE disease progression. Because A?42 and A?40 ameliorate experimental autoimmune inflammation targeting the CNS, we might now consider its potential anti-inflammatory role in other neuropathological conditions.

SUBMITTER: Grant JL

PROVIDER: S-EPMC3677069 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Reversal of paralysis and reduced inflammation from peripheral administration of β-amyloid in TH1 and TH17 versions of experimental autoimmune encephalomyelitis.

Grant Jacqueline L JL Ghosn Eliver Eid Bou EE Axtell Robert C RC Herges Katja K Kuipers Hedwich F HF Woodling Nathan S NS Andreasson Katrin K Herzenberg Leonard A LA Herzenberg Leonore A LA Steinman Lawrence L

Science translational medicine 20120801 145

β-Amyloid 42 (Aβ42) and β-amyloid 40 (Aβ40), major components of senile plaque deposits in Alzheimer's disease, are considered neurotoxic and proinflammatory. In multiple sclerosis, Aβ42 is up-regulated in brain lesions and damaged axons. We found, unexpectedly, that treatment with either Aβ42 or Aβ40 peptides reduced motor paralysis and brain inflammation in four different models of experimental autoimmune encephalomyelitis (EAE) with attenuation of motor paralysis, reduction of inflammatory le ...[more]

PMID: 22855462

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Dataset Information

Reversal of paralysis and reduced inflammation from peripheral administration of ?-amyloid in TH1 and TH17 versions of experimental autoimmune encephalomyelitis.

Publications

Reversal of paralysis and reduced inflammation from peripheral administration of β-amyloid in TH1 and TH17 versions of experimental autoimmune encephalomyelitis.

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