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 lesions in the central
nervous system (CNS), and suppression of lymphocyte activation. Aβ42 and
Aβ40 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 Aβ42 and Aβ40 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 Aβ peptide treatment. Protection conferred by
Aβ treatment did not require its delivery to the brain: Adoptive
transfer with lymphocytes from donors treated with Aβ42 attenuated EAE
in wild-type recipient mice, and Aβ deposition in the brain was not
detected in treated EAE mice by immunohistochemical analysis. In
contrast to the improvement in EAE with Aβ treatment, EAE was worse in
mice with genetic deletion of the amyloid precursor protein. Therefore,
in the absence of Aβ, there is exacerbated clinical EAE disease
progression. Because Aβ42 and Aβ40 ameliorate experimental autoimmune
inflammation targeting the CNS, we might now consider its potential
anti-inflammatory role in other neuropathological conditions.
Beta amyloid protein has been given as a vaccine to people with Alzheimers Disease in the hope that it generated a protective antibody response that inhibited Alzheimer plaque development. Using immunization of human proteins in mice it looked promising but putting human protein in humans, they sensitized humans to human beta amyloid and gave some people EAE. Therefore using such an approach in MS is going to carry a stigma of disaster. This study reports that giving a beta amyloid peptide can inhibit the development of brain inflammation through inhibition of the immune response. Whereas disease was worse in animals lacking beta amyloid precursor protein. Where it goes we shall see.
The reversal of paralysis claim is sort of a nonsense..reversal implies back to where you start from but this is just promotion of neurological recovery and if disease has developed the animals will not be same as they were before so reversal is a sloppy bit of terminology.
Labels: beta amyloid