The effects of ELF-MF on Aβ<sub>42</sub> deposition in AD mice and SWM-related neural oscillations

GENG Duyan; LIU Aoge; YAN Yuxin; ZHENG Weiran

doi:10.11999/JEIT241106

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GENG Duyan, LIU Aoge, YAN Yuxin, ZHENG Weiran. The effects of ELF-MF on Aβ42 deposition in AD mice and SWM-related neural oscillations[J]. Journal of Electronics & Information Technology. doi: 10.11999/JEIT241106

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GENG Duyan, LIU Aoge, YAN Yuxin, ZHENG Weiran. The effects of ELF-MF on Aβ₄₂ deposition in AD mice and SWM-related neural oscillations[J]. Journal of Electronics & Information Technology. doi: 10.11999/JEIT241106

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The effects of ELF-MF on Aβ₄₂ deposition in AD mice and SWM-related neural oscillations

doi: 10.11999/JEIT241106 cstr: 32379.14.JEIT241106

GENG Duyan^{1, 3
,
,},
LIU Aoge²,
YAN Yuxin¹,
ZHENG Weiran¹

1.
School of Electrical Engineering, Hebei University of Technology, Tianjin 300130, China
2.
School of Life Science and Health Engineering, Hebei University of Technology, Tianjin 300130, China
3.
State Key Laboratory of Reliability and Intelligence of Electrical Equipment, Hebei University of Technology, Tianjin 300130, China

Funds: The National Natural Science Foundation of China (52277230)

Received Date: 2024-12-16
Rev Recd Date: 2025-10-06

Available Online: 2025-10-20

Abstract

Abstract

Objective Extremely Low-Frequency Magnetic Fields (ELF-MF) have shown beneficial effects in various diseases; however, their influence on Alzheimer’s Disease (AD) remains insufficiently understood. With global population aging, AD has become one of the most prevalent neurodegenerative disorders. Its complex pathogenesis is characterized by neuronal loss, extracellular Amyloid-β (Aβ) deposition, and intracellular neurofibrillary tangles. Cognitive decline, particularly Spatial Working Memory (SWM) impairment, is among its main clinical manifestations. As a crucial cognitive function for encoding and retaining spatial location information, SWM underpins the execution of complex cognitive tasks. Impairment of SWM not only affects daily functioning but also serves as a key indicator of AD progression. Although previous studies have suggested potential cognitive benefits of ELF-MF exposure, systematic investigations integrating pathological, behavioral, and electrophysiological analyses remain limited. This study aims to investigate whether 40 Hz ELF-MF exposure mitigates AD pathology by assessing Aβ₄₂ deposition, SWM performance, and neural oscillatory activity in the hippocampal CA1 region, and to elucidate the relationships between electrophysiological modulation and behavioral improvement. Methods An integrated multidisciplinary approach combining immunofluorescence detection, behavioral assessment, and electrophysiological recording is employed. Transgenic AD model mice and Wild-Type (WT) controls are used and assigned to three groups: WT control (Con), AD model group (AD), and AD model group exposed to ELF-MF stimulation (ES). The ES group receives 40 Hz, 10 mT continuous pulse stimulation twice daily for 0.5 h per session over 14 consecutive days, whereas the AD and Con groups undergo sham stimulation during identical time periods. SWM is evaluated using the Object Location Task (OLT). Behavioral performance is quantitatively determined by calculating the Cognitive Index (CI), which reflects the animal’s capacity to recognize spatial novelty. During behavioral testing, Local Field Potential (LFP) signals are synchronously recorded from the hippocampal CA1 region via chronically implanted microelectrodes. Advanced signal processing techniques, including time-frequency distribution analysis and phase-amplitude coupling computation, are applied to characterize neural oscillations within the theta (4～13 Hz) and gamma (30～80 Hz) frequency bands. After completion of the experiments, brain tissues are collected for quantitative measurement of Aβ₄₂ plaque deposition in hippocampal sections through immunofluorescence staining, using standardized imaging and quantification protocols. Statistical analyses are performed to evaluate correlations between behavioral indices and electrophysiological parameters, with the objective of identifying mechanistic relationships underlying the effects of ELF-MF exposure. Results and Discussions Exposure to 40 Hz ELF-MF produced significant therapeutic effects across all examined parameters. Pathological analysis revealed markedly reduced Aβ₄₂ deposition in the hippocampal region of treated AD mice compared with untreated controls, supporting the amyloid cascade hypothesis, which identifies Aβ oligomers as critical triggers of neurodegeneration. This reduction suggests that ELF-MF may influence Aβ metabolic pathways, potentially through the regulation of mitochondrial dynamics, as reported in previous studies. Behavioral assessment indicated a pronounced improvement in SWM following ELF-MF exposure, reflected by significantly elevated CI scores in the OLT. Electrophysiological recordings revealed notable alterations in neural oscillatory activity, with treated animals exhibiting increased power spectral density in both theta (4～13 Hz) and gamma (30～80 Hz) bands during memory task performance. The temporal dynamics of theta oscillations also differed among groups: in Con and ES mice, peak theta power occurred approximately 0.5～1 seconds before the behavioral reference point, indicating anticipatory processing, whereas in AD mice, peaks appeared after the reference point, reflecting delayed cognitive responses. Cross-frequency coupling analysis further demonstrated enhanced theta-gamma phase-amplitude coupling strength in the hippocampal CA1 region of ELF-MF-exposed mice, with coupling peaks primarily observed in the lower theta and higher gamma frequencies. Correlation analyses revealed statistically significant positive relationships between behavioral cognitive indices and electrophysiological measures, particularly for theta power and theta-gamma coupling strength. These convergent findings across pathological, behavioral, and electrophysiological domains indicate that ELF-MF exposure may restore impaired neural synchronization mechanisms. Enhanced theta-gamma coupling is particularly relevant, as this neurophysiological mechanism is known to facilitate temporal coordination among neuronal assemblies during memory processing. Although the present study demonstrates clear benefits of ELF-MF stimulation, heterogeneity in previously reported results warrants consideration. The efficacy of ELF-MF appears highly dependent on key stimulation parameters such as frequency, intensity, duration, and exposure intervals. Previous studies have reported divergent effects, ranging from negligible or adverse outcomes to substantial cognitive enhancement under different experimental conditions. This parameter dependency presents challenges for clinical translation and highlights the need for systematic optimization in higher-order animal models. Conclusions This study demonstrates that exposure to a 40 Hz ELF-MF effectively reduces Aβ₄₂ deposition in the hippocampal region of AD mice, alleviates SWM deficits, and normalizes neural oscillatory activity in the hippocampal CA1 region. The observed cognitive improvements are closely linked to enhanced oscillations in the theta and gamma frequency bands and to strengthened theta-gamma cross-frequency coupling, indicating that neuromodulatory regulation of neural synchronization underlies behavioral recovery. These findings provide strong evidence supporting the potential of ELF-MF as a noninvasive therapeutic approach for AD, targeting both pathological markers and functional impairments. The study establishes a foundation for future work aimed at optimizing stimulation parameters and advancing translational applications, while highlighting the central role of neural oscillatory restoration as a therapeutic mechanism in neurodegenerative disorders. Further investigations should focus on refining exposure protocols and developing personalized stimulation strategies to accommodate individual variability in treatment responsiveness.
- Extremely Low-Frequency Magnetic Field (ELF-MF),
- Alzheimer’s Disease (AD),
- Spatial Working Memory (SWM),
- Neural oscillations,
- Amyloid-β (Aβ)

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