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Impairment of hippocampal gamma (γ)-frequency oscillations in vitro in mice overexpressing human amyloid precursor protein (APP)


Dr F. E. N. LeBeau, Institute of Neuroscience, Newcastle University, Medical School, Framlington Place, Newcastle-upon-Tyne, NE2 4HH, UK.


Alzheimer's disease is associated with a dramatic decline in cognitive performance including hippocampal-dependent memory. We have investigated one feature of hippocampal activity related to memory, the γ (30–80 Hz)-frequency rhythm. Hippocampal slices from mice overexpressing the human amyloid precursor protein (APP)SWE mutation (TAS10) were compared at 8 and 16 months of age with wild-type littermates. In slices obtained from TAS10 mice aged 8 months the γ-frequency activity evoked with bath application of 200 nm kainate was significantly (P < 0.05; n = 8 slices, five animals) impaired (area power, 5956 ± 2487 µV2) compared to slices from wild-type animals (area power, 18 256 ± 7880 µV2). At 16 months of age there was no longer a significant difference (P > 0.05; n = 11 slices from five animals) between slices from TAS10 and wild-type control mice as the wild-type mice now exhibited a marked age-dependent reduction in γ-frequency activity (TAS10 area power, 5751 ± 1573 µV2; wild-type area power = 5379 ± 1454 µV2). Although no dense-core plaques were evident at 8 months there was detectable amyloid labelling in the TAS10 mice which might account for the deficits in γ activity observed at this age. Dense plaques were clearly evident in the TAS10, but not wild-type, mice at 16 months of age but no further reductions in γ-frequency activity were seen in the TAS10 mice. These data suggest that deficits in network function in Alzheimer's disease occur early and are not directly correlated to amyloid load.