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June 14, 2026Neurobiology of DiseaseOpen Access

Alzheimer's 5XFAD mice show increased high-frequency oscillations and dysregulated rhythm coupling before overt plaque formation.

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Why the study?

Alzheimer disease is characterized by progressive neural network disruption, but sensitive electrophysiological markers of the earliest disease stages remain limited.

Population

5XFAD and wild-type mice at 1 month, 3-4 months, and 10-12 months

Comparison

5XFAD mice vs age-matched wild-type control mice

Design

Preclinical animal study

Key result

The 5XFAD mouse model of Alzheimer's disease showed increased high-frequency oscillation activity and dysregulated coupling to low-frequency rhythms preceding overt amyloid plaque formation.

Authors

PGPablo García-PeñaMRMilagros RamosJLJuan Manuel Montero López

Discussion

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Overview

Early iEEG abnormalities in pre-plaque 5XFAD mice suggest network biomarkers; hypothesis-generating and leaves human translation open.

Key Points

  • The aim is to identify early electrophysiological markers of network dysfunction in the 5XFAD mouse model of Alzheimer's disease.
  • iEEG recordings from 5XFAD and wild-type mice at 1, 3-4, and 10-12 months of age.
  • Analysis of spectral power distribution, epileptiform activity, and phase-amplitude coupling (PAC).
  • Comparison of electrophysiological features in young, adult, and old mice.
  • Young 5XFAD mice displayed increased high-frequency oscillation (HFO) power and altered PAC with low-frequency rhythms.
  • Adult 5XFAD mice exhibited prominent epileptiform activity and seizures alongside spectral alterations.
  • Old 5XFAD mice showed no significant differences in iEEG features compared to controls.

Structured PICO

P
Population
5XFAD and wild-type mice evaluated at 1, 3-4, and 10-12 months of age for intracranial EEG biomarkers of early network dysfunction.
E
Exposure
Intracranial EEG (iEEG) recordings to analyze spectral power distribution, epileptiform activity, and phase-amplitude coupling (PAC)
C
Comparator
Age-matched wild-type control mice
O
Outcome
Spectral power distribution, epileptiform activity, and phase-amplitude coupling (PAC)surrogate

Increased high-frequency oscillation activity and dysregulated coupling to low-frequency rhythms represent early electrophysiological signatures of network disruption in Alzheimer's disease prior to plaque formation.

Cite This Study

García-Peña et al. (2026) studied Alzheimer's disease. 5XFAD genotype vs. Wild-type mice was evaluated on Intracranial EEG spectral power distribution, epileptiform activity, and phase-amplitude coupling. The 5XFAD mouse model of Alzheimer's disease showed increased high-frequency oscillation activity and dysregulated coupling to low-frequency rhythms preceding overt amyloid plaque formation.

synapsesocial.com/papers/6a2e4524b1cc60ccdea8a6adhttps://doi.org/10.1016/j.nbd.2026.107484
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Disruption of electrophysiological rhythms and memory impairment in an Alzheimer’s transgenic rat model2025
  2. 2Reduced inhibition, bursting, and accelerated oscillations drive early hippocampal hyperactivity in Alzheimer’s disease in vivo2026
  3. 3Hippocampal and cortical activity reflect early hyperexcitability in an Alzheimer’s mouse model2025
  4. 4Abstract DP081: Impaired Electro-Calcium Coupling and Reduced Cerebral Blood Flow in the Early Stage of Alzheimer’s Disease2026
  5. 5Age dependent path integration deficit in 5xFAD mice2024 · 2 citations