Immunomodulation targeting of both Aβ and tau pathological conformers ameliorates Alzheimer’s disease pathology in TgSwDI and 3xTg mouse models

Journal of Neuroinflammation

Thomas Wisniewski⁴  Pankaj Mehta²  Yanjie Sun¹  Yong Ji³  Kinlung Wong¹  Daniel Peyser¹  Krystal Herline¹  Fernando Goñi¹ 

[1] Department of Neurology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA;New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Rd., Staten Island, NY 10314, USA;Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China;New York University School of Medicine, Alexandria ERSP, Rm 802, 450 East 29th Street, New York, NY 10016, USA

关键词: transgenic mice;    vaccination;    amyloid;    β-sheet conformation;    British amyloidosis;    Alzheimer’s disease;   

Others  :  834584
DOI  :  10.1186/1742-2094-10-150

 received in 2013-10-21, accepted in 2013-11-23,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Goñi et al.; licensee BioMed Central Ltd.

【 图 表 】

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