Abstract
Late Onset Alzheimer’s Disease is the most common cause of dementia, characterized by extracellular deposition of plaques primarily of amyloid-β (Aβ) peptide and tangles primarily of hyperphosphorylated tau protein. We present data to suggest a noninvasive strategy to decrease potentially toxic Aβ levels, using repeated electromagnetic field stimulation (REMFS) in primary human brain (PHB) cultures. We examined effects of REMFS on Aβ levels (Aβ40 and Aβ42, that are 40 or 42 amino acid residues in length, respectively) in PHB cultures at different frequencies, powers, and specific absorption rates (SAR). PHB cultures at day in vitro 7 (DIV7) treated with 64 MHz, and 1 hour daily for 14 days (DIV 21) had significantly reduced levels of secreted Aβ40 (p = 001) and Aβ42 (p = 0.029) peptides, compared to untreated cultures. PHB cultures (DIV7) treated at 64 MHz, for 1 or 2 hour during 14 days also produced significantly lower Aβ levels. PHB cultures (DIV28) treated with 64 MHz 1 hour/day during 4 or 8 days produced a similar significant reduction in Aβ40 levels. 0.4 W/kg was the minimum SAR required to produce a biological effect. Exposure did not result in cellular toxicity nor significant changes in secreted Aβ precursor protein-α (sAPPα) levels, suggesting the decrease in Aβ did not likely result from redirection toward the α-secretase pathway. EMF frequency and power used in our work is utilized in human magnetic resonance imaging (MRI, thus suggesting REMFS can be further developed in clinical settings to modulate Aβ deposition.
Highlights
Late Onset Alzheimer’s Disease is the most common cause of dementia, characterized by extracellular deposition of plaques primarily of amyloid-β (Aβ) peptide and tangles primarily of hyperphosphorylated tau protein
Our goal is to explore the use of noninvasive brain stimulation (NBS), such as repeated electromagnetic field stimulation (REFMS), as a potential non-invasive strategy to lower Aβ peptide load observed in Alzheimer’s disease (AD)
Cell membrane damage and integrity were measured by assaying lactate dehydrogenase (LDH) release into the conditioned medium (CM) in comparison to LDH present in cell lysates collected at the end of the experiment
Summary
Late Onset Alzheimer’s Disease is the most common cause of dementia, characterized by extracellular deposition of plaques primarily of amyloid-β (Aβ) peptide and tangles primarily of hyperphosphorylated tau protein. We present data to suggest a noninvasive strategy to decrease potentially toxic Aβ levels, using repeated electromagnetic field stimulation (REMFS) in primary human brain (PHB) cultures. Abbreviations AD Alzheimer’s disease APP Aβ precursor protein Aβ Amyloid-β BACE1 Beta-site APP cleaving enzyme 1 or β-Secretase CM Conditioned medium CSF Cerebrospinal fluid EOAD Early-onset FDA Food and Drug Administration PHB Primary human brain HSF1 Heat shock factor 1 IEC International Electrotechnical Commission IRB Institutional Review Board LDH Lactate dehydrogenase LOAD Late Onset Alzheimer’s Disease MRI Magnetic resonance imaging MSBE Minimum SAR with biological effect. The “anabolic” pathway wherein APP is processed first by one of the α-secretases, followed by γ-secretase activity, is neuroprotective and n eurotrophic[8,9,10,11,12]
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