Bibliographic
In this study the authors show that immunization with SDPM1, an Aβ1–40/42 amyloid binding and blocking peptide, reduces neuropathology and improves cognitive function in the APPswePSEN1(A246E) mouse model of Alzheimer’s disease. SDPM1 is a 20 amino acid peptide bounded by cysteines that binds tetramer forms of Aβ1–40- and Aβ1–42-amyloid and blocks subsequent Aβ amyloid aggregation. Immunization of mice with SDPM1 induced peptide mimotope antibodies with the same biological activity as the SDPM1 peptide. Immunization of Tg prior to the onset of beta amyloid plaque formation resulted in reduced beta amyloid plaque burden and Aβ1–40 and Aβ1–42 levels in the brain, improved cognitive performance in Morris water maze tests, and resulted in no increased T cell responses to immunogenic or Aβ peptides or brain inflammation. When done after plaque burden was already significant, SDPM1 immunization still significantly reduced amyloid plaque burden and Aβ1–40/1–42 peptide levels in Tg mice brain without inducing encephalitogenic T cell responses or brain inflammation, but treatment at this stage did not improve cognitive function These results demonstrate the efficacy of a novel vaccine approach for Alzheimer’s disease where immunization with an Aβ1–40/1–42 amyloid specific binding and blocking peptide is used to inhibit the development of neuropathology and cognitive dysfunction.