Affiliations: [a] Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada
| [b] Memorial University of Newfoundland, St. John’s, Newfoundland, Canada
Correspondence:
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Correspondence to: Scott H. Deibel, Memorial University of Newfoundland, 230 Elizabeth Ave, St. John’s, Newfoundland, A1C 5S7, Canada. Tel.: +1 709 864 8000; E-mail: [email protected].
Abstract: Circadian rhythm dysfunction is present in Alzheimer’s disease. Animal models of Alzheimer’s disease have been employed to investigate whether this dysfunction is a risk factor or symptom of the disease. The circadian phenotype in mouse models of Alzheimer’s disease is very disparate in terms of the degree and timing of the dysfunction. This is likely a result of some models elevating amyloid-β protein precursor instead of just the amyloid-β fragment present in human Alzheimer’s disease. We characterized activity rhythms in a novel knock-in mouse model (APPNL-G-F) of Alzheimer’s disease that elevates amyloid-β without overexpressing amyloid-β protein precursor. Despite increased rhythm amplitude, total activity, and a shortening of free-running period at 15 months of age, all other aspects of the activity rhythm were similar to controls from three to fifteen months of age. At two months of age, these mice were also able to entrain to a light-dark cycle with a period right on the edge of entrainment, which further suggests a healthy functioning circadian system. These data open the possibility that circadian rhythm disruptions in transgenic models of Alzheimer’s disease could be a result of these models having an artificial phenotype caused by overexpression of amyloid-β protein precursor.
