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. 1). 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.