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O4–05–07: FE65 amyloid precursor–protein binding proteins are essential for brain development
Author(s) -
Guenette Suzanne Y.,
Chang Yang,
Hiesberger Thomas,
Richardson James A.,
Christopher B.n.,
Eckman Elizabeth A.,
Hammer Robert E.,
Herz Joachim
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.333
Subject(s) - amyloid precursor protein , signal transducing adaptor protein , phenotype , knockout mouse , biology , microbiology and biotechnology , chemistry , pathology , biochemistry , alzheimer's disease , gene , medicine , signal transduction , disease
found in the brains of Alzheimer’s disease (AD) patients, and notably the presence of numerous neuritic amyloid plaques is required for a diagnosis of AD. There is a supporting evidence that soluble species of A play an important role in mediating initial pathological events in AD, and can provide a reliable predictor of developing dementia. Objective(s): To better understand the role of individual A peptides in dementia we have evaluated the cognitive status of novel BRI-A mice that over-express Ab in the absence of amyloid beta precursor protein (APP). Methods: BRIA 40 mice express 2-3 fold higher levels of A 1-40 than APP Tg2576 mice, but they do not develop A deposits even by 24 mo of age. BRI-A 42 mice, which showed 5-10 fold lower transgene expression than BRI-A 40 develop florid parenchymal and cerebrovascular A deposits by 3 mo of age in cerebellum and by 12 mo in forebrain. Changing A 42/ A 40 levels in APP transgenic mice through crossing Tg2576 mice with BRI-A mice we investigated their spatial learning and memory. Results: Behavioural evaluation of mice did not reveal any abnormalities in locomotor activity and motivation to explore novel environment. Furthermore, cognitive evaluation of the mice revealed that both explicit spatial reference memory evaluated in a water maze and implicit associative learning of taste aversion was not compromised in 14 -16 mo-old mice when the BRI-A 42 mice show extensive amyloid deposition. Conclusions: Amyloid load in the brain of BRI-A 42 mice was not associated with their cognitive performance, suggesting a dissociation between plaque number and cognition. Association between species of A levels in the brain of BRI-A and bigenic BRI-A xAPP mice and memory indices will be presented and discussed.