We investigated the therapeutic effects of two different versions of Aβ 1–15 (16) liposome-based vaccines. Inoculation of APP-V717IxPS-1 (APPxPS-1) double-transgenic mice with tetra-palmitoylated amyloid 1–15 peptide (palmAβ 1–15 ), or with amyloid 1–16 peptide (PEG-Aβ 1–16 ) linked to a polyethyleneglycol spacer at each end, and embedded within a liposome membrane, elicited fast immune responses with identical binding epitopes. PalmAβ 1–15 liposomal vaccine elicited an immune response that restored the memory defect of the mice, whereas that of PEG-Aβ 1–16 had no such effect. Immunoglobulins that were generated were predominantly of the IgG class with palmAβ 1–15 , whereas those elicited by PEG-Aβ 1–16 were primarily of the IgM class. The IgG subclasses of the antibodies generated by both vaccines were mostly IgG2b indicating noninflammatory Th2 isotype. CD and NMR revealed predominantly β-sheet conformation of palmAβ 1–15 and random coil of PEG-Aβ 1–16 . We conclude that the association with liposomes induced a variation of the immunogenic structures and thereby different immunogenicities. This finding supports the hypothesis that Alzheimer's disease is a “conformational” disease, implying that antibodies against amyloid sequences in the β-sheet conformation are preferred as potential therapeutic agents.
