Immunization with the SDPM1 peptide lowers amyloid plaque burden and improves cognitive function in the APPswePSEN1(A246E) transgenic mouse model of Alzheimer's disease

NEUROBIOLOGY OF DISEASE

卷:39

Article

Wang, Chiou-Miin¹  deVries, Sarah¹  Camboni, Marybeth¹  Glass, Matthew¹  Martin, Paul T.^1,2,3 

[1] Ohio State Univ, Ctr Gene Therapy, Res Inst, Nationwide Childrens Hosp,Coll Med, Columbus, OH 43205 USA

[2] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43205 USA

[3] Ohio State Univ, Coll Med, Dept Physiol & Cell Biol, Columbus, OH 43205 USA

关键词: Alzheimer's disease;    Aging;    Dementia;    Vaccine;    Peptide mimotope;    Memory;    Amyloid;   

DOI  :  10.1016/j.nbd.2010.05.013

来源: Elsevier

【 摘 要 】

Vaccination has become an important therapeutic approach to the treatment of Alzheimer's disease (AD), however, immunization with A beta amyloid can have unwanted, potentially lethal, side effects. Here we demonstrate an alternative peptide-mimotope vaccine strategy using the SDPM1 peptide. SDPM1 is a 20 amino acid peptide bounded by cysteines that binds tetramer forms of A beta(1-40)- and A beta(1-42)-amyloids and blocks subsequent A beta amyloid aggregation. Immunization of mice with SDPM I induced peptide-mimotope antibodies with the same biological activity as the SDPM1 peptide. When done prior to the onset of amyloid plaque formation, SDPM1 vaccination of APP5wePSEN1(A246E) transgenic mice reduced amyloid plaque burden and A beta(1-40) and A beta(1-42) levels in the brain, improved cognitive performance in Morris water maze tests, and resulted in no increased T cell responses to immunogenic or A beta peptides or brain inflammation. When done after plaque burden was already significant, SDPM I immunization still significantly reduced amyloid plaque burden and A beta(1-40/1-42) peptide levels in APPswePSEN1(A246E) brain without inducing encephalitogenic T cell responses or brain inflammation, but treatment at this stage did not improve cognitive function. These experiments demonstrate the efficacy of a novel vaccine approach for Alzheimer's disease where immunization with an A beta(1-40/1-42) amyloid-specific binding and blocking peptide is used to inhibit the development of neuropathology and cognitive dysfunction. (C) 2010 Elsevier Inc. All rights reserved.

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