Vaccination has become an important therapeutic approach to the treatment of 
Alzheimer's disease (AD), however, immunization with Abeta 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 Abeta(1-40)- and 
Abeta(1-42)-amyloids and blocks subsequent Abeta amyloid aggregation. 
Immunization of mice with SDPM1 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 APPswePSEN1(A246E) transgenic 
mice reduced amyloid plaque burden and Abeta(1-40) and Abeta(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 Abeta peptides or brain 
inflammation. When done after plaque burden was already significant, SDPM1 
immunization still significantly reduced amyloid plaque burden and 
Abeta(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 Abeta(1-40/1-42) amyloid-specific binding and blocking peptide is used 
to inhibit the development of neuropathology and cognitive dysfunction.