Published in:
Open Access
01-12-2013 | Research
Immunomodulation targeting of both Aβ and tau pathological conformers ameliorates Alzheimer’s disease pathology in TgSwDI and 3xTg mouse models
Authors:
Fernando Goñi, Krystal Herline, Daniel Peyser, Kinlung Wong, Yong Ji, Yanjie Sun, Pankaj Mehta, Thomas Wisniewski
Published in:
Journal of Neuroinflammation
|
Issue 1/2013
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Abstract
Background
Central to the pathogenesis of Alzheimer’s disease (AD) and many other neurodegenerative diseases is the conformational change of a normal self-protein into toxic oligomeric species and amyloid deposits. None of these disorders have an effective therapy, but immunization approaches hold great promise. We have previously shown that active immunization with a novel peptide when polymerized into a stable oligomeric conformation, pBri, induced a humoral immune response to toxic Aβ species in an AD model, APP/PS1 transgenic (Tg) mice, reducing plaque deposits. pBri is a glutaraldehyde polymerized form of the carboxyl fragment of an amyloidogenic protein, which is deposited in the brains of patients with a rare autosomal dominant disease due to a missense mutation in a stop codon, resulting in the translation of an intronic sequence, with no known sequence homology to any mammalian protein.
Methods
In the current study we tested whether pBri-peptide-based immunomodulation is effective at reducing both vascular amyloid deposits and tau-related pathology using TgSwDI mice with extensive congophilic angiopathy and 3xTg mice with tau pathology.
Results
Our results indicate that this immunomodulation approach, which produces a humoral response to proteins in a pathological conformation, is effective at reducing both Aβ and tau-related pathologies.
Conclusions
This immunomodulatory approach has the advantage of using a non-self-immunogen that is less likely to be associated with autoimmune toxicity. Furthermore we found that it is able to target all the cardinal features of AD concurrently.