NeuroEM for Alzheimer’s

NeuroEM now markets their PEMF device they spent 15 years developing under the name  Wavium. Wavium is a consumer wellness brand for people who want to support cognitive performance today while taking a more proactive approach to long-term brain health. The Wavium headset is designed for consumer wellness use and does not require a prescription. NeuroEM has some pretty impressive interim results of clinical trials. Decreases in cortisol and increases in creatine phosphate, a backup for ATP, are given as possible mechanisms.

This post explores a “mechanistic” mouse study of NeuroEM’s device for treating Alzheimer’s Disease. [1] It should be noted that the Assisi radio frequency PEMF device was designed to target the Ca²⁺ calmodulin interaction. The Neuro EM device appears to target complex IV of the mitochondrial electron transport chain. A diurnal component of very low frequency PEMF has been presented in the Schumann Resonance post. The really interesting about this study is that the time of day seems to influence body and brain temperatures in transgenic and neurotypical mice. Fast forward to low sample size human clinical trials, things look very different. The post ends by bringing in a very biophysical review. Things are promising and so very complicated.

Cell phones, mitochondria, Arendash 2010

“Despite numerous studies, there is no definitive evidence that high-frequency electromagnetic field (EMF) exposure is a risk to human health. To the contrary, this report presents the first evidence that long-term EMF exposure directly associated with cell phone use (918 MHz; 0.25 w/kg) provides cognitive benefits. Both cognitive-protective and cognitive-enhancing effects of EMF exposure were discovered for both normal mice and transgenic mice destined to develop Alzheimer’s-like cognitive impairment. The cognitive interference task utilized in this study was designed from, and measure-for-measure analogous to, a human cognitive interference task. In Alzheimer’s disease mice, long-term EMF exposure reduced brain amyloid-beta (Abeta) deposition through Abeta anti-aggregation actions and increased brain temperature during exposure periods. Several inter-related mechanisms of EMF action are proposed, including increased Abeta clearance from the brains of Alzheimer’s disease mice, increased neuronal activity, and increased cerebral blood flow. Although caution should be taken in extrapolating these mouse studies to humans, we conclude that EMF exposure may represent a non-invasive, non-pharmacologic therapeutic against Alzheimer’s disease and an effective memory-enhancing approach in general.”

Alzheimer mutations

A quick image of the Amyloid Precursor Protein being cleaved into peptides that form the amyloid plaques associated with Alheimer’s Diease.

The familial Alzheimer’s Disease mice used in Arendash publications

All mice in these studies were derived from The Florida Alzheimer’s Disease Research Center’s colony. Each mouse had a mixed background, that is to say, pretty out bred and hopefully more resembling a typical human except that it has the so called “Swedish Mutation”

APP K670N, M671L gene (APPsw) also known as the Swedish Mutation, is the only known mutation immediately adjacent to the β-secretase site in APP. The mice in this study were heterozygous for the Swedish APP mutation.

All mice were maintained on a 12 h dark and 12 h light cycle with ad libitum access to rodent chow and water. Mention was not made of access to exercise wheels. It is assumed that the mice were sedentary. See the last section on Circadian Rhythms and Radical pair mechanism.

Other Alzheimer’s Mutations Yan 2024

Yan 2024 identified two mitochondrial-related candidate genes associated with mild cognitive impairment and late onset Alzheimer’s Disease: NDUFA1 and NDUFS5,

• NDUFA1 is a the gene coding for NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1, of Complex I
• NDUFS5 NADH dehydrogenase [ubiquinone] iron-sulfur protein 5, also part of complex I.
• PSEN1, presenillin, is a sub unit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP.  interferes with the function of the γ-secretase complex, which alters the processing of the APP and leads to the overproduction of a longer, toxic version of Aβ peptide (Aβ42) Click to view a cartoon. The Martín-Maestro paper in Yan 2024 has been reviewed in the PSEN1 and mitophagy post.
• apolipoprotein The Mutations in the APOE4 variant are associated with the most common late onset familial and sporadic forms of Alzheimer’s Disease. ApoE is basically a lipid particle transporter. The human genome as three alleles 2,3, 4 Blades 2024 recently published a report showing Impaired cellular copper regulation in the presence of ApoE4 by virtue of inhibition of the copper export protein ATP7A. The graphical abstract of this publication says much.

Let’s not forget Tau and neurofibrillary tangles, Rowat 2022

“Alzheimer’s disease (AD) is the leading cause of dementia in elderly people. Amyloid beta (Aβ) deposits and neurofibrillary tangles are the major pathological features in an Alzheimer’s brain. These proteins are highly expressed in nerve cells and found in most tissues. Tau primarily provides stabilization to microtubules in the part of axons and dendrites. However, tau in a pathological state becomes hyperphosphorylated, causing tau dysfunction and leading to synaptic impairment and degeneration of neurons. This article presents a summary of the role of tau, phosphorylated tau (p-tau) in AD, and other tauopathies. Tauopathies, including Pick’s disease, frontotemporal dementia, corticobasal degeneration, Alzheimer’s disease, argyrophilic grain disease, progressive supranuclear palsy, and Huntington’s disease, are the result of misprocessing and accumulation of tau within the neuronal and glial cells. This article also focuses on current research on the post-translational modifications and genetics of tau, tau pathology, the role of tau in tauopathies and the development of new drugs targeting p-tau, and the therapeutics for treating and possibly preventing tauopathies.” Just from reading the abstract, post translational modifications are just as important as mutations in genes, though this review covered Tau mutations. Hyperphosphorylated tau participates in other nuerodegereative diseases.

Perhaps the take home is that healthy mitochondria mean less work for lysosomes that degrade amyloid and/or tau neurofibrillary tangles? Here is a link to a Maverick cartoon of lysosome duties: degrading spent receptors, degrading exogenous proteins, and getting rid of dysfunctional mitochondria.

Dragicevic 2011, cell phone makes FAD mitochondria healthier

GW Arendash is the corresponding author. This study focused on cell phone EMF and the mitochondria in Familial Alzheimer’s Disease mice. Keeping mitochondria healthy means that lysosomes can focus on degrading amyloids.

the protocol

The mice were exposed to two 1-h sessions of PREMF per day (early morning and late
afternoon).

• 918 MHz, involved modulation with Gaussian minimal-shift keying (GMSK)signal, and was non-continuous
• carrier bursts repeated every 4.6 ms, 217 Hz
• electrical field 17 – 35 V/m.
• SAR levels that varied between 0.25 and 1.05 W/kg.

the results

parameter	neurotypical	transgenic	comment
basal (State II)	slight ⇑ in cortex & hippocampus	slight ⇑ in cortex, hippocampus	Basal with pyruvate and malate as electron source (substrate)
maximum (State V)	slight ⇑ in cortex & hipppocampus	slight ⇑ in cortex, hippocampus	maximum respiration, no H+ grad, complex IV inhib
reserve cont ratio	no change	⇑ all four nothing under 2	< 2 for RCR indicate poorly coupled mitochondria.
mitochondrial ROS	no change	no change str amy	PEMF prevents 2x ROS in cortex hippocampus
membrane potential	no change	⇑ in cortex & hippocampus	biggest ⇑ hippocampus
mito ATP	no change	⇑ in cortex, hippocampus striatum	largest ⇑ hippocampus
Complex IV activity	very slight ⇑ in cor hip str	⇑ in cortex, hippocampus striatum	>2x ⇑ hip
Body morning	35.5oC, 37oC	36oC, 37oC	PEMF ⇑ temp
noon between experiments	36oC,	36oC,	PEMF no change
late afternoon	36oC, 37oC	36oC, 37oC	PEMF ⇑ temp
brain morning	35.5oC, 35.5oC	36.5oC, 34oC	PEMF ⇓ Temp Tg
noon between exp	36oC-36oC	36oC-36oC	lots of variability
late afternoon	36oC, 36oC	36.oC, 34oC	not quite sig ⇓

The story will continue with more Arendash Lab publications. Later it was shown that radio frequencies do not really change brain temps in actual humans, Arendash 2025.

comment on human mitochondrial diurnal variations van Moorsel 2023

On the opposite of the familial AD spectrum, a Dutch study examined the muscle mitochondrial respiration in Caucasian males in their 20s. The expected variation in body temperature was observed, Diurnal changes were seen in BMAL, Clock, and PER2. State 3 respiration with a variety of different substrates was maximal by late afternoon with a significant dawn to dusk increase. State 5 uncoupled (maximal) respiration appear to increase but was not statistically significant. There was no real change in the activity of individual complexes. Nor was there a decrease in the dawn to dusk lever of PINK. There was, however a dawn to dusk decrease in mitochondrial fusion protein OPA-1 and mitochondrial fission protein FIS-1.

PREMF promotes β-amyloid dissolution Arendash 2012

This follow up study used the same model and protocol as the first except that there were short term (12 days) and long term (2 month) treatment spans.

results

• PREMF improved the performance in the Y-maze for both the Nt and Tg mice.
• Working memory tests showed promise but were not as conclusive
• Brain and body temperatures were monitored over the course of six weeks. PREMF increased both body and brain temps in the Nt but did not ncrease these temperatures as much in the Tg mice.
• PREMF decreased regional cerebral blood flow at 2 months and at 12 days. This was particularly true in Tg mice whether the PREMF was on or off. Literature was cited claiming that soluble/monomeric Aβ is a powerful vasoconstrictor.
• In the 2 month Tg group PREMF decreased the Aβ deposition in both hippocampus and entorhinal cortex

comment on copper Sarell 2009, Arendash 2012

Sarell 2009 measured the affinity of Cu²⁺ for both monomeric and fibrillar Abeta(1-42) using two independent methods. The authors examined pH dependency of copper binding and side chains involved. They concluded an extremely high “pico molar” affinity. Does PREMF somehow encourage the release of copper from these aggregates?

In 2012 Gary Arendash wrote an excellent review on work done at the time. There are some excellent images in this publication that describe the previous studies. It is proposed that PREMF breaks up amyloid complexes.

• This review goes into great detail as to how safe this radio frequency range is.
• This review does mention PBT2, a metal chelator that suppresses metal-induced Aβ oligomerization.
• Dr Arendash reasoned that very low frequency PEMF can have deleterious effects whereas the radio frequency PEMF had not at the time of publication shown to have any biological effect. Ironically, humans are exposed to these every day with their cell phones.
• Dr Arendash cited studies showing exposure of rats to the 25-50 Hz range caused deficits in the performance of the Morris water maze.
• Mechanism(s) of NeuroEM are up regulated heat shock proteins and transthyretin. Transthyretin is an Aβ-binding protein increased by cellphone usage. Dr Arendash, back in 2012, established three different mechanisms for the cellphone frequency PEMF.

An 8 patient pilot study breaking up p-tau & Aβ_1-42 Arendash 2019

• All eight patients had ApoE genotypes of 2/3 or 3/3. No ApoE4. The genetic cause, if known, was not disclosed.
• pulsed fashion and sequentially through the 8 emitters at 915 MHz carrier frequency every 4.6 ms (e.g., a pulse repetition rate to each antenna of 217 Hz). Power levels (specific absorption rate, SAR) for each emitter were set at an average of 1.6 W/kg. 
• 60 day treatment
• Cognitive tests demonstrated meaningful improvement.
• FDG-PET analysis, “anatomic” MRI scans from pre-treatment (Baseline) and post-treatment (Day 60) were selected. FDG is a fluorine radioactive analog of glucose that is used to measure which parts of the brain have the best glucose uptake. The participates were stable in terms of glucose utilization with a few showing improvement.
• CSF and blood samples were analyzed for soluble/monomeric Aβ_1-40 and Aβ_1-42, oligomeric Aβ, total tau (t-tau), and p-tau. PREMF produced increases in cerebrospinal fluid (CSF) levels of soluble Aβ_1-40 and Aβ_1-42, cognition-related changes in CSF oligomeric Aβ, a decreased CSF p-tau/Aβ_1-42 ratio, and reduced levels of oligomeric Aβ in plasma.

We’re going to learn that radio frequencies act on hydrogen bonding networks, Perez 2024. NMR findings of Potnuru 2026 show that phosphorylation within the tau fibril core promotes fibril registry and stability through water-mediated, hydrogen-bonded phosphoryl wires.  Lee 2016 conducted a Molecular Dynamics computer simulation of the in water and the hydropobic compound DMSO. The “salt-bridge of Asp23 and Lys28 in Aβ1-42 was the key for amyloid folding based on the various analysis including hydrogen bond, electrostatic interaction energy and salt-bridge distance. Since this salt-bridge region plays a crucial role in initiating the misfolding of Aβ1-42.”

⚖ ️Arendash 2022, balancing cytokines, mining the first study Cao 2022

Did the PREMF increase cognitive scores and glucose utilization just by reducing inflammation and such as that? The CSF and blood samples were analyzed for twelve cytokines.

• Table 2, no significant changes in cytokines
• Those that had the highest starting cytokines showed the greatest improvements in those cytokines after PREMF treatment.

However TABLE 3. Low vs. high baseline cytokine/growth factor levels in plasma demonstrated highly significant changes.

Progressing to a 2½-year study. Arendash 2022

• This group of five AD patients also had ApoE mutations.
• Fig 2 gives a diagram of this on , off, on again schedule that lasted for over two years.
• No declines in cognitive scores. It should be noted that untreated controls were not used in this study.
• PREMF was associated with reductions in the CSF levels of C-reactive protein, p-tau217, Aβ1-40, and Aβ1-42 while modulating CSF oligomeric Aβ levels.
• In the plasma, modulated/rebalanced levels of both p-tau217 and total tau were observed.

Vascular endothelial growth factor Arendash 2019, 2024

The authors reanalyzed old plasma and CSF samples to find a strong baseline correlation between VEGF levels and AD markers (t-tau, p-tau, Aβ_1-40, Aβ_1-42) These markers were reduced by the by the treatment. Reduction in these markers correlated with increases in VEGF levels in AD subjects with low or not measurable “baseline” VEGF levels. These increased VEGF levels were associated with increased clearance/drainage of tau and Aβ from the brain, likely through VEGF’s actions on meningeal lymphatic vessels (mLVs)

Fig. 1 A model to explain the removal of Aβ

• mLVs are located within the brain’s meninges/dura, Figure 1 gives a nice diagram.
• mLVs drain half of total brain CSF and are a site for a substantial amount of toxin drainage/clearance from the brain. CSF
• The location of the PREMF emitters relative to these drainages were given in Fig1.

Fig. 2

• Dilation of mLVs and their proliferation are controlled by VEGF.
• Likely sources of VEGF: choroid plexus ependymal cells, epithelial ependymal cells lining the choroid plexus, resident macrophages within the choroid

PEMF increases VEGF production in a skeletal muscle ischemia model described in the PEMF eNOS PI3K post.

PREMF, mitochondria, tubulin: NeuroEM past and present

This post has covered miochondria and pulsed radiofrequency electromagnetic fields (PEMF). Perez 2025 is a collaboration between, gerontologist Dr Filipe Perez MD and electrical and bio engineers. Previous work from the group was cited using what appears to be a homemade device. This team that are focused on getting deeper penetration’s of the PREMF. The team also has a strong grasp of physical chemistry with hydrogen bonding getting a lot of page space. In reference to Baranowski 2025 showing the lack of brain heating, they focused on non-thermal mechanisms of PREMF. NCBI/structure allows the user to color residues according to charge. Charged residues can H-bond to water and each other. Not addressed as much in the Prez review (Perez 2024) is the electrostatic interactions of charged surfaces with ions in solution. Arendash 2026 added that microtubules are filled with semi-crystallin water meaning that waters were in well organized structures.

So what do microtubules have to do with mitochondria? Puurand 2019 suggested that microtubules not only transport mitochondria to areas of high energy demand in muscle and the brain, but also interact with the voltage dependent anion channel VDAC. It is tubulin monomers, that is, that interact with miochondria. This link will take the reader to a summary cartoon.

“In recent decades, there have been several models describing the relationships between the cytoskeleton and the bioenergetic function of the cell. The main player in these models is the voltage-dependent anion channel (VDAC), located in the mitochondrial outer membrane. Most metabolites including respiratory substrates, ADP, and Pi enter mitochondria only through VDAC. At the same time, high-energy phosphates are channeled out and directed to cellular energy transfer networks. Regulation of these energy fluxes is controlled by β-tubulin, bound to VDAC. It is also thought that β-tubulin‒VDAC interaction modulates cellular energy metabolism in cancer, e.g., switching from oxidative phosphorylation to glycolysis. In this review we focus on the described roles of unpolymerized αβ-tubulin heterodimers in regulating VDAC permeability for adenine nucleotides and cellular bioenergetics. We introduce the Mitochondrial Interactosome model and the function of the βII-tubulin subunit in this model in muscle cells and brain synaptosomes, and also consider the role of βIII-tubulin in cancer cells.” (Puurand 2019)

In July of 2026 Gary Arendash published a 27 figure review that concentrated on his work of radio frequencies with an added microtubule twist. Fig 18 is interesting in that it correlates mitochondrial energy production and the GTP needed for microtubule polymerization. (GTP, ATP, and creatine phosphate are pretty interchangeable.) It did not address monomers binding to βII-tubulin. Fig 27 is a summary of everything in the review: radio frequencies vibrate in the microtubules, and break up Aβ and p-tau oligomers.

References

• Arendash GW, Sanchez-Ramos J, Mori T, et al (2010) Electromagnetic field treatment protects against and reverses cognitive impairment in Alzheimer’s disease mice. J Alzheimers Dis 19 191–210: PubMed
• Arendash GW. Transcranial electromagnetic treatment against Alzheimer’s disease: why it has the potential to trump Alzheimer’s disease drug development. J Alzheimers Dis. 2012;32(2):243-66. free paper
• Arendash GW, Mori T, Dorsey M, Gonzalez R, Tajiri N, Borlongan C. Electromagnetic treatment to old Alzheimer’s mice reverses β-amyloid deposition, modifies cerebral blood flow, and provides selected cognitive benefit. PLoS One. 2012;7(4):e35751. PMC free paper
• Arendash G, Cao C, Abulaban H, Baranowski R, Wisniewski G, Becerra L, Andel R, Lin X, Zhang X, Wittwer D, Moulton J, Arrington J, Smith A. A Clinical Trial of Transcranial Electromagnetic Treatment in Alzheimer’s Disease: Cognitive Enhancement and Associated Changes in Cerebrospinal Fluid, Blood, and Brain Imaging. J Alzheimers Dis. 2019;71(1):57-82. PMC free paper
• Arendash G, Abulaban H, Steen S, Andel R, Wang Y, Bai Y, Baranowski R, McGarity J, Scritsmier L, Lin X, Shen N, Aljassabi A, Li Y, Cao C. Transcranial Electromagnetic Treatment Stops Alzheimer’s Disease Cognitive Decline over a 2½-Year Period: A Pilot Study. Medicines (Basel). 2022 Aug 3;9(8):42. PMC free paper
• Arendash GW, Lin X, Cao C. Enhanced Brain Clearance of Tau and Amyloid-β in Alzheimer’s Disease Patients by Transcranial Radiofrequency Wave Treatment: A Central Role of Vascular Endothelial Growth Factor (VEGF). J Alzheimers Dis. 2024;100(s1):S223-S241. free paper
• Arendash GW. Neuronal Microtubules and Radiofrequency Waves: The Quantum Core of Human Consciousness, Memory, and Pathway to Memory Enhancement/Recovery. Int J Mol Sci. 2026 Jul 7;27(13):6090. PMC free paper
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• Cao C, Abulaban H, Baranowski R, Wang Y, Bai Y, Lin X, Shen N, Zhang X, Arendash GW. Transcranial Electromagnetic Treatment “Rebalances” Blood and Brain Cytokine Levels in Alzheimer’s Patients: A New Mechanism for Reversal of Their Cognitive Impairment. Front Aging Neurosci. 2022 May 2;14:829049. PMC free paper
• Dragicevic N, Bradshaw PC, Mamcarz M, Lin X, Wang L, Cao C, Arendash GW. Long-term electromagnetic field treatment enhances brain mitochondrial function of both Alzheimer’s transgenic mice and normal mice: a mechanism for electromagnetic field-induced cognitive benefit? Neuroscience. 2011 Jun 30;185:135-49. . free paper
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