046.08 / O6 - Neither sleep disruption nor induced cortical plasticity precipitates the onset of amyloid-β pathology in an Alzheimer’s disease mouse model: preliminary data from a study of sleep and plasticity as risk factors

Alzheimer’s disease is frequently modelled by transgenic mice overproducing the amyloid-beta (Aβ) peptide, which causes fibrillar deposits to accumulate by 4 months of age. In this exploratory study, the effects of increased production and impaired clearance of Aβ on the onset of Aβ deposition was examined. Weekly alternating-row mystacial whisker trimming was intended to induce cortical plasticity, while a moderate sleep disruption protocol, eight hours on an orbital shaker platform activated for 15-45 seconds at random intervals averaging two minutes for three non-consecutive nights a week, was intended to disrupt clearance (Kang et al., 2009; Sinton et al., 2009). At eight weeks of age, 12 male and 12 female APPswe/PS1dE9 mice were assigned to four groups subjected to whisker trimming or sham, and sleep disruption or sham, in all combinations, for one month. Aβ was labelled immunohistochemically using MOAB2 to show oligomeric accumulations preceding the appearance of fibrillar pathology, and epifluorescence images were segmented using the unbiased ImageSURF machine learning plugin to quantitate the amount of Aβ deposits in the cerebral cortex. The total observed deposition was very small (below 0.5% in all conditions), and linear mixed effects models indicated that neither manipulation had a significant effect (p > 0.05 for all effects and interactions). Sex differences were not assessed, although high spontaneous death rates in female animals unrelated to experimental conditions required replacement from additional cohorts. We conclude that induced plasticity and mild sleep disruption are insufficient to hasten the onset of pathology in an overexpressing mouse model. Ongoing studies are examining the effect of several months’ manipulation on animals aged six and nine months.