A p. vaccination of a genetic model of Alzheimer's disease

摘要

Alzheimer's disease (AD), the pathological hallmarks of which are amyloid plaques, neuroflbrittary tangles and neuronal loss, is the most common dementia in elderly persons. To date, much evidence supports the hypothesis that the excess extracellular deposition of amyloid p-peptide (Ap) is the most likely initiator of the pathogenesis of the disease. Recently, immunization of Ap in PDAPP transgenic mouse model of AD was reported to reduce the burden of amyloid in the central nervous system. We show here that immunization results in an ~ 50% reduction in dense-core amyloid plaques and an improvement in cognitive impairment in both the young and old TgCRNDS murine model of AD, without changing the total amount of Ap in the brain. The induced sera had strong immunoreactivity with dense-cored Ap plaques, not with the amyloid precursor protein, and reduced Ap fibril formation and cytotoxicity of Ap in vitro.