ABSTRACT
Objective To test the hypothesis that high frequency oscillations (HFOs) between 250 and 500Hz occur in mouse models of Alzheimer’s disease (AD).
Methods Experiments were conducted in three mouse models of AD: Tg2576 mice (n=9) that overexpress the Swedish mutation of amyloid precursor protein, presenilin 2 knock-out (PS2KO) mice (n=8), and the Ts65Dn model of Down’s syndrome (n=9). We recorded HFOs using wideband (0.1-500Hz, 2kHz) intra-hippocampal and cortical surface EEG at 1month until 24months of age during wakefulness, slow wave sleep (SWS) and rapid eye movement (REM) sleep. EEG was also recorded using the intra-hippocampal kainic acid and pilocarpine models of epilepsy to compare HFOs in AD and epilepsy models. Interictal spikes (IIS) and seizures in the AD models were also analyzed for the possible presence of HFOs.
Results We describe for the first time hippocampal and cortical HFOs as a new EEG abnormality in AD mouse models. HFOs occurred in all transgenic mice and but no controls (p<0.05). HFOs were most frequent during SWS (vs. REM or wakefulness, p<0.05). HFOs in the AD and epilepsy models were indistinguishable in both spectral frequency and duration (p>0.05). HFOs also occurred during IIS and seizures in the AD models, although with altered spectral properties compared to isolated HFOs (p<0.05).
Interpretation Our data demonstrate a new EEG biomarker in AD mouse models which is detectable from the scalp and thus amenable to non-invasive detection in people at risk for AD.
Competing Interest Statement
The authors have declared no competing interest.
Abbreviations
- AD
- Alzheimer’s disease
- HFOs
- High frequency oscillations
- IHKA
- Intra-hippocampal kainic acid
- IIS
- Interictal spike
- PILO
- Pilocarpine
- PS2KO
- Presenilin 2 knock-out
- REM
- Rapid eye movement sleep
- SWS
- Slow wave sleep