Dampened slow oscillation connectivity anticipates amyloid deposition in the ps2app mouse model of alzheimer’s disease

To fight Alzheimer’s disease (AD), we should know when, where, and how brain network dysfunctions initiate. In AD mouse models, relevant information can be derived from brain electrical activity. With a multi-site linear probe, we recorded local field potentials simultaneously at the posterior-parietal cortex and hippocampus of wild-type and double transgenic AD mice, under anesthesia. We focused on PS2APP (B6.152H) mice carrying both presenilin-2 (PS2) and amyloid precursor protein (APP) mutations, at three and six months of age, before and after plaque deposition respectively. To highlight defects linked to either the PS2 or APP mutation, we included in the analysis age-matched PS2.30H and APP-Swedish mice, carrying each of the mutations individually. Our study also included PSEN2^−/− mice. At three months, only predeposition B6.152H mice show a reduction in the functional connectivity of slow oscillations (SO) and in the power ratio between SO and delta waves. At six months, plaque-seeding B6.152H mice undergo a worsening of the low/high frequency power imbalance and show a massive loss of cortico-hippocampal phase-amplitude coupling (PAC) between SO and higher frequencies, a feature shared with amyloid-free PS2.30H mice. We conclude that the PS2 mutation is sufficient to impair SO PAC and accelerate network dysfunctions in amyloid-accumulating mice.