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O1‐05‐05: A novel immunotherapy reverses cognitive deficits in a preclinical model of amyloid pathology
Author(s) -
Evans Charles E.,
Thomas Rhian S.,
Kidd Emma J.,
Good Mark A.
Publication year - 2015
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2015.07.055
Subject(s) - cognition , cognitive decline , medicine , novelty , neuroscience , psychology , endocrinology , dementia , disease , social psychology
mice. cSNK vaccination was assessed in AD mouse models treated at 3 months of age with monthly vaccination and then evaluated at 13 months of age. Results:A monoclonal antibody raised against this novel epitope (5E3) binds to synthetic Ab oligomers (AbO), but is unreactive to monomeric and fibrillar Ab, as well as to amyloid plaques. 5E3 is effective at blocking AbO behavioural toxicity in vivo in wild type mice. Moreover acute treatment with 5E3 reduced AbO concentration in CSF and brains of aged APP/PS1 and Tg2576 mice, with no apparent impact on pre-existing plaques. Furthermore, cSNK-vaccinated mice produced an AbO specific immune response, without cross-reactivity to Ab monomers. Conclusions: These experiments demonstrate three important findings: 1) murine 5E3 can neutralize the toxicity of synthetic AbOs in the molecular weight range of AbOs previously implicated in synaptic dysfunction; 2) systemically administered 5E3 demonstrates target engagement for AbOs in two mouse models of Alzheimer disease in vivo; and 3) active vaccination with the cSNK epitope generates AbO reactivity in mice without recognition of other Ab molecular species. Together, our data demonstrates that cSNK is a well-defined AbO-specific epitope with therapeutic potential.