Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease

C Janus, J Pearson, JA McLaurin, PM Mathews… - Nature, 2000 - nature.com
C Janus, J Pearson, JA McLaurin, PM Mathews, Y Jiang, SD Schmidt, MA Chishti, P Horne…
Nature, 2000nature.com
Much evidence indicates that abnormal processing and extracellular deposition of amyloid-β
peptide (Aβ), a proteolytic derivative of the β-amyloid precursor protein (βAPP), is central to
the pathogenesis of Alzheimer's disease (reviewed in ref.). In the PDAPP transgenic mouse
model of Alzheimer's disease, immunization with Aβ causes a marked reduction in burden of
the brain amyloid,. Evidence that Aβ immunization also reduces cognitive dysfunction in
murine models of Alzheimer's disease would support the hypothesis that abnormal Aβ …
Abstract
Much evidence indicates that abnormal processing and extracellular deposition of amyloid-β peptide (Aβ), a proteolytic derivative of the β-amyloid precursor protein (βAPP), is central to the pathogenesis of Alzheimer's disease (reviewed in ref. ). In the PDAPP transgenic mouse model of Alzheimer's disease, immunization with Aβ causes a marked reduction in burden of the brain amyloid,. Evidence that Aβ immunization also reduces cognitive dysfunction in murine models of Alzheimer's disease would support the hypothesis that abnormal Aβ 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 Aβ immunization reduces both deposition of cerebral fibrillar Aβ and cognitive dysfunction in the TgCRND8 murine model of Alzheimer's disease without, however, altering total levels of Aβ in the brain. This implies that either a ∼50% reduction in dense-cored Aβ plaques is sufficient to affect cognition, or that vaccination may modulate the activity/abundance of a small subpopulation of especially toxic Aβ species.
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