A learning deficit related to age and b-amyloid plaques in a mouse model of Alzheimer's disease
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Date
21/12/2000Author
Chen, Guiquan
Chen, Karen S
Knox, Jane H
Inglis, Jennifer
Bernard, Andrew
Martin, Stephen J
Justice, Alan
McConlogue, Lisa
Games, Dora
Freedman, Stephen B
Morris, Richard G M
Metadata
Abstract
Mice that overexpress the human mutant amyloid precursor
protein (hAPP) show learning deficits, but the apparent lack of
a relationship between these deficits and the progressive b-amyloid
plaque formation that the hAPP mice display is puzzling.
In the water maze (1), hAPP mice are impaired before and after
amyloid plaque deposition (2-7). Here we show, using a new watermaze
training protocol, that PDAPP mice (8) also exhibit a separate
age-related deficit in learning a series of spatial locations. This
impairment correlates with b-amyloid plaque burden and is
shown in both cross-sectional and longitudinal experimental
designs. Cued navigation and object-recognition memory are
normal. These findings indicate that Ab overexpression and/or
Ab plaques are associated with disturbed cognitive function and,
importantly, suggest that some but not all forms of learning and
memory are suitable behavioural assays of the progressive cognitive
deficits associated with Alzheimer's-disease-type pathologies.