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A beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease.

Janus C., Pearson J., McLaurin J., Mathews P.M., Jiang Y., Schmidt S.D., Chishti M.A., Horne P., Heslin D., French J., Mount H.T., Nixon R.A., Mercken M., Bergeron C., Fraser P.E., St George-Hyslop P., Westaway D.

Much evidence indicates that abnormal processing and extracellular deposition of amyloid-beta peptide (A beta), a proteolytic derivative of the beta-amyloid precursor protein (betaAPP), is central to the pathogenesis of Alzheimer's disease (reviewed in ref. 1). In the PDAPP transgenic mouse model of Alzheimer's disease, immunization with A beta causes a marked reduction in burden of the brain amyloid. Evidence that A beta immunization also reduces cognitive dysfunction in murine models of Alzheimer's disease would support the hypothesis that abnormal A beta processing is essential to the pathogenesis of Alzheimer's disease, and would encourage the development of other strategies directed at the 'amyloid cascade'. Here we show that A beta immunization reduces both deposition of cerebral fibrillar A beta and cognitive dysfunction in the TgCRND8 murine model of Alzheimer's disease without, however, altering total levels of A beta in the brain. This implies that either a approximately 50% reduction in dense-cored A beta plaques is sufficient to affect cognition, or that vaccination may modulate the activity/abundance of a small subpopulation of especially toxic A beta species.

Nature 408:979-982(2000) [PubMed] [Europe PMC]