EEG, activity, and sleep architecture in a transgenic AβPPswe/PSEN1A246E Alzheimer's disease mouse.
Since sleep and electroencephalogram (EEG) disturbances are endophenotypes of Alzheimer's disease (AD) patients alongside cognitive dysfunction, we here characterized these parameters in transgenic mice carrying transgenes for amyloid-β protein precursor (AβPPswe) and presenilin 1 (PSEN1A246E) at 5 (pre-plaque) and 20 months, relative to PSEN1 and wild-type (WT) mice, using a novel wireless microchip device. While circadian rhythms were not affected, we obtained significantly higher overall activity at 5 months in the AβPP/PSEN1 strain (p < 0.001) compared to both PSEN1 and WT animals. Vigilance staging revealed that AβPP/PSEN1 animals present with an age-independent increase in wakefulness (p < 0.001) and a decrease in non rapid-eye movement (NREM) sleep (p < 0.01). These changes were age- and genotype-dependent only during the light phase, while dark phase activity pattern were equally affected at both ages. In all genotypes, the amount of REM sleep was lower at 20 months indicating a general age-related profile. Spectral power of qEEG changed in AβPP/PSEN1 mice at 5 months during wakefulness and REM sleep; during wakefulness hippocampal delta (0.5-5 Hz) was reduced and theta (5-9 Hz) power enhanced. By contrast, NREM EEG spectra were affected by age and genotype. Interestingly, PSEN1 animals also showed spectral EEG changes, these differed from both WT and AβPP/PSEN1 animals. Our results indicate that AβPP/PSEN1 mice exhibit abnormalities in activity and sleep architecture preceding amyloid plaque deposition as well as age-related changes in cortical EEG power. Though not fully recapitulating the profile of AD patients, this suggests activity and EEG recordings as sensitive and translational biomarkers in murine models.
Jyoti
Amar
A
School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, Scotland, UK.
Plano
Andrea
A
Riedel
Gernot
G
Platt
Bettina
B
D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D004569:Electroencephalography / Q000379:methods; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D053764:Presenilin-1 / Q000235:genetics*; D012890:Sleep / Q000502:physiology*
D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1