β-Amyloid peptide is widely held to have a deleterious role in Alzheimer’s disease. β-Amyloid 42 (Aβ42) and β-amyloid 40 (Aβ40), major components of senile plaque deposits in Alzheimer’s disease, are considered neurotoxic and proinflammatory.
Therefore it is an unexpected surprise that Grant and coworkers report that treatment with either Aβ42 or Aβ40 peptides reduced motor paralysis and brain inflammation in four different models of experimental autoimmune encephalomyelitis (EAE). Experimental autoimmune encephalomyelitis is an accepted animal model of multiple sclerosis. Specifically, attenuation of motor paralysis, reduction of inflammatory lesions in the central nervous system (CNS), and suppression of lymphocyte activation were seen. Major proinflammatory cytokines and chemokines were reduced in the blood after Aβ peptide treatment and protection conferred by Aβ treatment did not require its delivery to the brain. Anti-inflammatory effects of Aβ appear to be dependent on immune cells because treatment was also successful in models of experimental autoimmune encephalomyelitis caused by transplantation of pathogenic T cells.
By contrast, experimental autoimmune encephalomyelitis symptoms were worse in mice with genetic deletion of the amyloid precursor protein. The absence of β-amyloid therefore appeared to exacerbate clinical experimental autoimmune encephalomyelitis disease progression. The authors suggest that β-amyloid may have therapeutic potential in diseases such as multiple sclerosis. More research is needed to understand why β-amyloid is deleterious in Alzheimer’s disease and the mechanisms underlying its potentially therapeutic action for multiple sclerosis.
Grant JL, Ghosn EE, Axtell RC, Herges K, Kuipers HF, Woodling NS, Andreasson K, Herzenberg LA, Herzenberg LA, Steinman L: Reversal of Paralysis and Reduced Inflammation from Peripheral Administration of β-Amyloid in TH1 and TH17 Versions of Experimental Autoimmune Encephalomyelitis. Sci. Transl. Med. 4, 145ra105 (2012).
See also: Focus: Multiple Sclerosis β-Amyloid: Enemy or Remedy?