SKIN-PATCH VACCINATION AGAINST ALZHEIMER'S DISEASE

Alzheimer's disease (AD) and inclusion body myositis (IBM) share a number of common pathologies such as deposits of amyloid beta-protein (AB) and paired helical filaments, although such pathologies are mostly restricted to brain for AD and to muscle for IBM. Transgenic mice (Tg 13592) that express the 99-amino acid carboxyl-terminal fragment (C99) of AB precursor in the brain and skeletal muscle develop pathologies remarkably similar to those in IBM and show memory deficits resembling the early stages of AD. Induction of an immune response in several animal models of AD by repeated needle injection or nasal administration with synthetic A13 has prevented or reduced AD-like pathology and memory deficits. The long-term objective is to evaluate the efficacy of topical application (skin-patch) of vector-based vaccines in the prevention and treatment of AD and IBM. The Specific Aims are to construct adenovirus vectors encoding all or part of AB or C99 and to determine serum titers against the antigens in the Tg13592 mice immunized by the skin-patch. The procedure eliminates problems associated with needle injections, requires no specially trained personnel and equipment, and so may reduce medical costs. This novel vaccination modality may have benefit to patients with these diseases and commercial value.