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P4‐037: Novel age‐dependent learning deficits in a mouse model of Alzheimer's disease: Implications for translational research
Author(s) -
Montgomery Karienn S.,
Simmons Rebecca K.,
Edwards George A.,
Nicolle Michele M.,
Gluck Mark A.,
Myers Catherine E.,
Bizon Jennifer L.
Publication year - 2009
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.2009.04.907
Subject(s) - hippocampal formation , neuroscience , psychology , cognition , recall , morris water navigation task , stimulus (psychology) , alzheimer's disease , disease , cognitive psychology , developmental psychology , medicine
motor functions. Methods: Line 1 mice over-expressing a gene coding for human truncated tau (amino acids 295-390 combined with an N-terminal signal sequence) were bred on an NMRI background. Female, homozygous transgenic mice aged w4 and 11 months were assessed in two different open field water maze paradigms and compared with age-matched wild-type controls. In the spatial reference memory task (A), the hidden platform is maintained in its location throughout learning. By contrast, in the spatial problem-solving task (B), an initial visual pre-training is followed by training to a hidden platform until a criterion is met, then the platform changes location and animals are trained until the next criterion is met, and then repeated. Results: The spatial reference memory task (A) did not reveal any age-related spatial learning deficit since neither elderly controls nor transgenic mice were able to acquire the task. Given the progressive accumulation of tau in the transgenic mice during ageing, however, one would expect them to perform worse than wild-type animals. In the alternative, problem solving task (B), a cognitive impairment in NMRI-derived transgenic mice was observed. Although aged mice were impaired visually and motorically in the visible platform test relative to young mice, there was no genotype difference. When trained to criterion, tau transgenic mice required longer to learn the location of the platform and, over a set acquisition period, achieved fewer platform locations. Conclusions: These findings indicate that there is a learning deficit in these mice that is related to transgene expression but which is not due to visual or motor impairment. The line 1 mouse provides a model for the study of cognitive dysfunction in tauopathies and an important tool for investigating the mechanism underlying neurodegeneration and cognitive impairment in age-related neurodegenerative disease.