P1–081: Learning and memory changes in Tg2576 transgenic mice: A longitudinal study

Le résumé fourni par la source

The Tg2576 mouse model of Alzheimer's disease (mice overexpressing the ″Swedish″ mutation in the human amyloid precursor protein 695) exhibits elevated brain levels of soluble Aβ1–40/42by 6–8 months of age and age–dependent increase in the amount of amyloid plaques in the neocortex and hippocampus by 9 months. The behavioral phenotyping of Tg2576 animals revealed some cognitive impairments compared to age–matched non–transgenic control, however the results of behavioral tests are contradictory and the number of studies using animals over 10 months has been restricted. In the present study a cognitive characterization of transgenic and wild type control male mice was performed at 6, 9, 12, 15, 18 and 22 months of age. The change of spontaneous alternation performance and place recognition memory in Y–maze and spatial learning in the Morris water maze were assessed. The Tg2576 mice showed a moderate impairment in the spontaneous alternation over all ages tested compared to nontransgenic control, furthermore an increased activity of the Tg2576 mice manifested in the higher number of arm entries in the Y–maze. In the place recognition test both transgenic and wild–type mice produced a delay–dependent short term memory deficit. However, the 15–month–old Tg2576 animals at 30 min delay exhibited reduced place recognition and by 18 months of age their performance significantly differed from that of nontransgenic control already at 15 min delay. The Morris water maze test was performed at 18 months of age. Both transgenic and wild–type mice showed similarly long escape latencies in the hidden and visible platform test. Our data indicate that spontaneous alternation impairment may be independent from plaque generation, however it can be in connection with the presence of soluble amyloid or can reflect a transgene–associated effect. The disruption in the place recognition developed in old transgenic mice can be a sensitive marker of cognitive decline in this mouse model of Alzheimer′s disease.

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