Open AccessProgressive cognitive decline in a transgenic mouse model of Alzheimer's disease overexpressing mutant hAPPswe
Author(s) -
Middei S.,
Daniele S.,
Caprioli A.,
Ghirardi O.,
AmmassariTeule M.
Publication year - 2006
Publication title -
genes, brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.315
H-Index - 91
eISSN - 1601-183X
pISSN - 1601-1848
DOI - 10.1111/j.1601-183x.2005.00160.x
Subject(s) - habituation , novelty , genetically modified mouse , hippocampus , neuropathology , neuroscience , cognition , hippocampal formation , amyloid precursor protein , cognitive decline , amyloid (mycology) , psychology , barnes maze , alzheimer's disease , dementia , transgene , medicine , disease , biology , pathology , biochemistry , gene , social psychology , spatial learning
The possibility of detecting progressive changes in cognitive function reflecting the spatio‐temporal pattern of β‐amyloid peptide (Aβ) deposition was investigated in Tg2576 mice overexpressing the human mutant amyloid precursor protein (hAPP). Here, we show that at 7 months of age, Tg2576 mice exhibited a selective deficit in hippocampus‐based operations including a defective habituation of object exploration, a lack of reactivity to spatial novelty and a disruption of allothetic orientation in a cross‐shaped maze. At 14 months of age, Tg2576 mice displayed a more extended pattern of behavioral abnormalities, because they failed to react to object novelty and exclusively relied on motor‐based orientation in the cross‐shaped maze. However, an impaired reactivity to spatial and object novelty possibly reflecting age‐related attention deficits also emerged in aged wild‐type mice. These findings further underline that early cognitive markers of AD can be detected in Tg2576 mice before Aβ deposition occurs and suggest that as in humans, cognitive deterioration progressively evolves from an initial hippocampal syndrome to global dementia because of the combined effect of the neuropathology and aging.