The aim of the present work was to develop an easy, safe and effective vaccine in Balb/c mice using the Aβ 1–15 peptide as immunogen entrapped in PLGA microparticles to reduce the risk of an adverse T cell-mediated response. Aβ 1–15, which contains the N-terminal antibody epitope of the full Aβ 1–42 peptide was encapsulated in PLGA by a modified solvent evaporation/extraction technique using a double emulsion system. Microparticles were characterized in terms of size distribution (1.22±0.28μm), encapsulation efficiency (75.05±4.17%), surface associated peptide (59.81±0.96%) and “in vitro” release profile. Balb/c mice were immunized by subcutaneous and intranasal routes with three 30μg doses of the peptide microencapsulated in PLGA. A solution of the peptide alone and an emulsion in the Freund’s adjuvant were administered subcutaneously as control groups. Antibody levels elicited against the toxic Aβ 1–40 fraction in the serum of PLGA microparticles treated groups were higher than that of the peptide alone groups. Our initial results indicate that immunotherapy with Aβ 1–15 loaded PLGA microparticles could be a promising approach for the future development of a safe vaccine against Alzheimer’s disease.