Slow-wave-modulated high-frequency oscillations reveal early network abnormalities in pre-pathological 5XFAD mice.

Area of Science:

• Neuroscience
• Electrophysiology
• Biomarkers

Background:

• Alzheimer's disease (AD) involves progressive neural network disruption and abnormal brain oscillations.
• Sensitive electrophysiological markers for early AD stages are limited.
• The 5XFAD mouse model exhibits amyloid-beta accumulation preceding plaque formation.

Purpose of the Study:

• Investigate intracranial EEG (iEEG) biomarkers for early network dysfunction in the 5XFAD mouse model of AD.
• Focus on electrophysiological changes in the pre-plaque stage of AD pathology.
• Identify sensitive markers for early-stage Alzheimer's disease.

Main Methods:

• Recorded iEEG from 5XFAD and wild-type mice at young, adult, and old ages.
• Analyzed spectral power, epileptiform activity, and phase-amplitude coupling (PAC).
• Correlated electrophysiological findings with histopathological markers of AD.

Main Results:

• Young 5XFAD mice, despite lacking plaques, showed reduced low-frequency power and increased high-frequency oscillation (HFO) power.
• Adult 5XFAD mice exhibited similar spectral changes, plus epileptiform activity and seizures.
• Pathological HFO activity was linked to altered PAC with slow oscillations, emerging before plaque deposition.

Conclusions:

• Increased HFO activity and dysregulated PAC are early electrophysiological signatures of cortical hyperexcitability in AD.
• These markers precede amyloid plaque formation and neurodegeneration.
• Combined HFO power and PAC metrics show translational potential as early AD biomarkers.