Aβ vaccination of a genetic model of Alzheimer's disease

Alzheimer's disease (AD), the pathological hallmarks of which are amyloid plaques, neurofibrillary 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 β-peptide (Aβ) is the most likely initiator of the pathogenesis of the disease. Recently, immunization of Aβ 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 TgCRND8 murine model of AD, without changing the total amount of Aβ in the brain. The induced sera had strong immunoreactivity with dense-cored Aβ plaques, not with the amyloid precursor protein, and reduced Aβ fibril formation and cytotoxicity of Aβ in vitro. These findings suggest that immunization may be a potential therapy, although undesirable immune reactions must be avoided.