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 beta-peptide (Abeta) is the most likely initiator of the pathogenesis of the disease. Recently, immunization of Abeta 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 similar to 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 Abeta in the brain. The induced sera had strong immunoreactivity with dense-cored Abeta plaques, not with the amyloid precursor protein, and reduced Abeta fibril formation and cytotoxicity of Abeta in vitro. These findings suggest that immunization may be a potential therapy, although undesirable immune reactions must be avoided. (C) 2003 Published by Elsevier Science B.V.