Spectroscopic investigation of tau protein conformational changes by static magnetic field exposure

Electromagnetic fields taint the molecular environment of proteins and induce changes in the central nervous system. This research applied Fourier transform infrared spectroscopic analysis to investigate the effects of static magnetic fields on tau protein in neurological disorders. It explores the conformational changes of tau protein and highlights its’ potential application as a pathological biomarker for early detection and therapeutic interventions. The results indicate that tau protein is susceptible to magnetic field exposure in the amide B, fingerprint, and amide regions (IV-VI). Changes in peak positions and band intensities were identified and delineated as the outcome effect of magnetic forces on molecular vibrations. Magnetic forces may affect the microtubule structure of the tau protein, leading to protein aggregation. These results indicate the potential application of FTIR spectroscopy for the early detection and classification of degenerative diseases through spectrum analysis. Different magnetic fields can be used as spontaneous therapeutic procedures to induce changes in the molecular environment of proteins.

the last decade, several studies indicated that moderate TSMF in the range between 1 mT and 1 T can affect human cortical excitability [4]. TSMF has been used as a noninvasive brain stimulation technique, but more investigations are needed to understand these mechanisms [5][6][7]. Another area of scientific concern is whether exposure to static magnetic fields causes DNA damage or not. Past studies have confirmed that a static magnetic field alone has no such effect on the fundamental properties of cell growth and survival under standard culture conditions. However, there is an indication that the frequency of micronucleus formation changes substantially when specific treatments such as X-irradiation and mitomycin C are used during exposure to a strong static magnetic field. Several studies have suggested that a strong static magnetic field may influence ion transport and gene expression. Other studies have found that a strong magnetic field can cause spatial orientation phenomena in cell culture [8]. Moreover, protein misfolding and aggregation are becoming fingerprints of neurodegenerative diseases, including Alzheimer's, Huntington's, Parkinson's, prion diseases, and amyotrophic lateral sclerosis [9]. Protein misfolding and aggregation are natural phenomena that disrupt cell function through many mechanisms that are yet to be fully explained [10,11].
In 2002, The International Agency for Research on Cancer (IARC) revealed that extremely low frequency (ELF) magnetic fields are 'possibly carcinogenic to humans' [12][13][14][15]. Most of the neural activities in the brain are processed through electrical impulses. Consequently, it is possible that exposure to a static magnetic field (SMF) can yield physiological and biochemical alterations. However, there is a lack of unanimity regarding the effects of SMF on different proteins; it appears that SMF induces physiological changes in exposed proteins. These changes can either improve biological tasks or cause dysfunction depending on the amount of absorbed energy by the proteins [16][17][18][19][20].
Tau is a microtubule-associated protein that has an essential role in axonal stabilization, neuronal development, and neuronal polarity [21]. It composes cytoskeletons which are crucial in maintaining spine development and morphology, brain cognitive behavior, consciousness, and memory storage [22]. These skeletons form a tube-shaped where nutrients and other substances are carried through into the neurons. Tau proteins are intrinsically disordered due to their unstable conformation and high pliability [23]. The role of tau protein is to maintain healthy neurons through reversible polymerization of microtubules formations to maintain neural growth and neural polarity [24]. Figure 1 illustrates the function of Tau protein in keeping neurons healthy [25].
Tau protein determinations and quantifications are essential to the diagnosis of most degenerative diseases. Early detections of tau protein changes based on biomarkers may allow earlier diagnosis for most infectious and autoimmune diseases [26]. Researchers are becoming more convinced that Alzheimer's disease (AD) may result from a combination of abnormal tau and beta-amyloid proteins associated with other age-related diseases such as cerebrovascular and Lewy body [27]. Analysis of several brain tissues from AD patients confirmed two different abnormal formations of extra neural amyloid plaques and intraneural tangles containing fibrillary structure mainly composed of microtubule Tau protein [27][28][29][30][31].
It seems that neuropathologic diagnosis of AD cases correlates to the formation of both filamentous tau protein and cored neuritic plaques [32]. The tau filaments are called 'paired helical filaments' (PHFs). They reveal reparative patterns as viewed through electron microscopy showing two tiny filaments twisted around one another, forming periodic structures with a 65-80 nm crossover distance. On the other hand, neuritic plaques are composed of activated microglia and reactive astrocytes entangled with neuritic elements in the plaque periphery [27]. In other words, the abnormal aggregation of tau protein into insoluble paired helical filaments (PHFs) is one of the indications of AD [33]. It appears that intracellular inclusions of fibrillar forms of tau protein with β-sheet structure assemble in specific brain regions, causing memory loss. Besides, pathological studies using animals and humans have shown that tau oligomer formation contributes to neuronal loss [23]. Microtubule-associated protein tau belongs to the expanding group of natively unfolded proteins or intrinsically disordered proteins (IDPs), which can display novel features in protein chemistry.
Furthermore, histological analysis and tau positron emission tomography (PET) imaging studies have disclosed that cognitive impairment correlates with tau presence and neuronal loss in the human brain and its associations with aging and AD [34]. It suggests that tau oligomers formation and grey matter loss lead to cognitive deficits by different mechanisms, suggesting implications for future therapeutic trials targeting tau pathology [35]. Another analysis suggests that aggregation of hyperphosphorylated forms of tau in the neural soma forming neurofibrillary tangles may constitute the leading cause of AD [36]. Heiko and Eva Braak have shown that tau deposits of neurofibrillary tangles follow a particular pathway in their proliferating from the trans entorhinal cortex to neocortical association areas and finally to secondary and primary cortical areas. They suggested six disease stages where the first two stages are asymptomatic, the following two stages show some cognitive ability loss, and the last two stages are associated with dementia [37].
Previous studies have shown that the vibration modes of the amide bands exhibit high sensitivity when exposed to ELF-electromagnetic fields [38,39]. Protein conformational changes are observed because of the effects on vibrational modes of the amide bands in proteins in the IR region of the spectrum [40]. Fouriertransform infrared (FTIR) spectroscopy is a noninvasive technique to detect changes in the secondary structure of proteins and has been widely used to investigate protein oligomerization, aggregation, and fibril formation [10,11]. A considerable amount of research linked protein conformational changes to the molecular vibration of the absorption bands of the secondary structure in the studied proteins. These changes can be detected through the spectrum variations in the mid-infrared range (400-4000 cm −1 ). FTIR is a sensitive diagnostic tool to differentiate abnormalities in biological cells. The biochemical changes in cells often correspond to changes in the fingerprint regions of the proteins.
The present study will investigate the impact of exposing tau protein to SMF by FTIR spectroscopy. The experimental setup aims to imitate neuronal proteins' exposure to SMF, similar to what happens in the brain by passing neuron signals. A considerable amount of scientific research has revealed a strong connection between band intensities and their peak positions of the IR spectra to the secondary structure changes of the studied proteins [41][42][43].
Studies of the effects of SMF on different proteins could open new perspectives in health research, especially in the applicability of immunosensor development in clinical diagnosis. Several studies have used biological samples obtained from patients with neurodivergent conditions to confirm the application of immune sensors through the time-dependent phase angle shift technique Single Frequency Analysis (SFA), which is based on the phase angle shift from antibody-antigen interactions [44].
Early detection of tau oligomers formation through absorbed infrared energy can be used as a sensor to detect certain diseases' early stages accurately. The absorbance spectrum in the Mid-infrared region for a tissue or blood sample is considered a unique way to represent the contents of the sample. The unknown sample is easily identified by comparing the obtained fingerprint spectrum to a library of known spectra. The analysis of the measured spectra can provide insights into physiological and pathological changes that have taken place at the molecular level.

Preparation of stock solutions
Tau protein contains six recombinant tau proteins expressed in E. coli, with molecular weights of 36.8, 39.7, 40.0, 42.6, 42.9, and 45.9 kDa. The proteins are expressed without histidine tags. The purity of each protein is >90% (SDS-PAGE). The six Tau isoforms differ from one another by the number (3 or 4) of microtubulebinding repeats (R) of 31-32 amino acids each and the number (0, 1, or 2) of amino-terminal inserts (N) of 29 amino acids each [45]. Tau protein is supplied as a solution in 125 mM Tris-HCl, pH 6.8, with 4% SDS, 10% 2-mercaptoethanol, 20% glycerol, and 0.004% bromophenol blue. Each sample of 50 ml of the tau protein ladder contains 0.25 mg of each of the six isoforms.
The Tau protein samples were obtained from Sigma Aldrich Chemical Company. The samples were kept at −20°C without any further purification prior to their use. Samples solutions were incubated for one hour at room temperature, then the samples were prepared for measurement. 50 ml of each aqueous sample was positioned on a silicon window plate and was left to dry completely at room temperature prior to taking spectroscopic measurements.

FTIR spectroscopic measurements
Bruker IFS 66/S spectrophotometer equipped with a liquid nitrogen-cooled Mercury-Cadmium-Telluride (MCT) detector and KBr beam splitter was used to scan the FTIR measurements. The spectrophotometer was continuously purged with dry air to reduce the noise signal. Each spectrum was obtained by taking an average of 60 repeated scans to maintain measurement accuracy. The FTIR measurements were obtained at a spectral resolution of 4 cm −1 , and the aperture setting was held at 8 mm, which gives the best signal-to-noise ratio. OPUS software is used to accurately make the baseline corrections, the second derivatives of the spectra, and peak position identifications. The Fourier self-deconvolution (FSD) process decomposes the major absorption bands into the original constituents of each individual peak, which correspond to the vibrational modes of molecules in the protein's secondary structure. All FSD processes were consistently repeated six times. The FTIR spectra of tau protein were scanned in the featured region of (4000-400) cm −1 . The background's absorption spectrum was consistently subtracted from the sample's spectrum from each of the FTIR spectra. The net effect of the static magnetic field on the tau protein, represented by the difference spectra, was calculated by subtracting the sample's spectrum before exposure to the magnetic field from the sample's spectrum after exposure. As an accuracy check, the resulting difference spectra of the featureless region of the protein spectra (1800-2200) cm −1 , must always give zero difference. In addition, control samples with the same protein concentration difference spectra resulted in a flat line formation as expected.

Static magnetic field measurements
DC voltage regulated at 220 volts and connected to an electromagnetic coil was used to produce a static magnetic field. The prepared sample was placed as close as possible to the center of the coil at a fixed holder. This sample positioning ensures that the magnetic field is uniform and perpendicular to the sample's surface. The Tau sample experienced the following various magnetic fields: 0.0, 0.24, 0, 48, 0.6, 0,9, 0.45, 1.2, 1.8, 2.2 mT. Each sample was exposed to each magnetic field setting for 2.0 min. The value of each magnetic field was taken for each measurement using a magnetic field axial probe PHYWE Gauss meter.

Results
The experimental results were obtained by analysis of FTIR absorption spectra for tau protein over the entire mid-infrared region (4000-400) cm −1 as shown in figure 2(A). At the same time, the second derivative of the absorption spectrum is shown in figure 2 The FTIR spectra were obtained for Tau Protein before and after the exposure to different static magnetic fields while keeping the sample fixed in its position all the time. This approach allows for precise comparison of band intensities and peak positions before and after exposing the protein to the different static magnetic fields.
The FSD absorbance spectra of the tau protein showed detailed structure for the significant absorption bands including, all amide bands and the fingerprint region. The absorption peaks in the amide I region (1600-1700) cm −1 correspond to the stretching vibrations of the C=O coupled with C-N stretching and C-C-N deformation mode [46].
Several peaks are shown in the amide II region (1480-1600) cm −1 due to the out-of-plane merger of N-H inplane bending and C-N stretching vibration [47]. The absorption bands in the amide III region (1220-1320) cm −1 are composed of an in-plane mixture between the N-H bending and the C-N stretching with extra contributions from the C-H and the N-H deformation vibrations [47,48]. The absorption bands in the amide IV region (625-770) cm −1 correspond to the vibration linked to a mixture of OCN bending vibrations coupled with out-of-plane N-H bending [49]. In the amide V region (640-800) cm −1 , the absorption bands are due to out-of-plane N-H bending, while the absorption bands in the VI region (537-606) cm −1 are due to out-of-plane C=O bending [50]. The absorption bands in the region (900-1220) cm −1 are assigned to C-O bending vibrations of saccharides (glucose, lactose, and glycerol) [51]. Furthermore, the absorption bands in the region (1360-1430) cm −1 are due to the vibrations of specific amino acid chains, while the absorption bands in the range of (1430-1480) cm −1 are caused by fatty acids, phospholipids, and triglycerides [52].
All the prominent seen peaks of the absorption bands before and after exposure to magnetic fields in the mid-infrared spectral range (400-4000) cm −1 are assigned according to the second derivative, and the FSD computations are listed in table 1. The FSD absorption spectra of tau protein show the main absorption bands, including the amide bands and the fingerprint regions.
The spectra in figure 3 for the range of (500-1000) cm −1 show a remarkable increase in most bands' intensities due to the exposure to the static magnetic field.
Moreover, peak shifts with minor changes in the band structures were observed in some cases, indicating high sensitivity to the magnetic field. The peak at 583 cm −1 merged with the neighboring peak at 594 cm −1 after the magnetic field exposure. The bands at (595 and 612) cm −1 have tripled in their intensities, and the peak at 612 cm −1 shifted to 620 cm −1 . The peak at 632 cm −1 decreased in intensity and appeared as a shoulder with the neighboring band at 650 cm −1 as the magnetic field strength increased. The peak at 669 cm −1 did not change, while the peaks at 683, 704, and 719 have shown a small increase in their intensities. The peak at 737 cm −1 reduced its intensity sharply and disappeared, while the peak at 800 cm −1 increased its intensity suddenly after exposure to the magnetic field. The remaining peak' changes are listed in table 1. The FSD spectra in the ranges of (1000-1700) cm −1 and (1700-4000) cm −1 are shown in figure 4 and figure 5 respectively. All changes in band intensities and peak positions are listed in table 1 and table 2. Consistently, the resultant effect of the magnetic field on the tau protein is determined by subtracting the tau protein's spectrum before exposure to the magnetic field from the spectrum after the exposure. The difference spectra for the range (500-1700) cm −1 is shown in figure 6(C), which reveals all the affected absorption bands by the exposure to the SMF.

Discussion
The experimental results of exposing tau protein to SMF have shown changes in the measured absorption spectra. These changes are related to changes in the secondary structure of tau protein and are indicated by band position, band intensity, and bandwidth variations for most of the observed bands. The peaks' changes are usually linked to a shift in the absorbed frequency due to external effects on the vibrational bonds. The frequency of vibration of the normal mode excited by the absorbed light is expressed by equation (1).  Where ν is the frequency in (cm −1 ), k is the force constant in N cm −1 , and μ is the reduced mass in kg. The only changing variables in the equation are k and μ. These two molecular variables determine the absorbed infrared frequency by any molecule. No two different molecules have the same force constants and atomic masses, so each chemical structure's infrared spectra must differ. It seems that any protein conformation can alter the frequency of the absorbed energy due to modifications in the original bond vibrations of the absorption band. Therefore, it is reasonable to expect that protein aggregation instigates a decrease in the frequency of the secondary structure vibrations [9]. The intensity of the absorption bands in the infrared spectra depends on the concentration of molecules in the sample, as shown by Beer's law in equation (2), which relates the concentration to the absorbance.
Where A is absorbance, ε is absorptivity, � is path length, and c is concentration. Any variation in the number of bonds is directly connected to conformational changes in the protein's structure and can affect absorbance. Furthermore, the intensities of IR bands can be enhanced by increasing the number of dipole moments of the macromolecules because of their alignment to the applied field. The increase in intensities is proportional to the square of the variation of the dipole moment of the molecule induced by vibrations, as shown by equation (3) [56], the intensity I k between the vibrational state E k and the ground state E 0 is Where N is Avogadro's number, R α,k is the transition dipole moment between the states 0 and k in the αdirection, E 0, and E k is the first and the (k+1) th eigenvalues. The dipole moment depends on the distance separating the charge; for example, C-H stretching is more intense than C-C rock vibration. The frequencies of stretching vibration are higher than their corresponding bending frequencies, and bonds to hydrogen have higher stretching frequencies than other heavier atoms.
The intensity is related to the substance's temperature and the quantum mechanical interaction between the radiation and the absorber. Therefore, determining absolute intensities is a complicated task. Most researchers calculate the integrated intensities by integrating the area under the absorption bands-to indicate relative changes in the intensities. Any changes in the absorption bands of proteins indicate conformational changes in those proteins due to charge or vibrational changes. The most substantial effect occurs when the magnetic field is perpendicular to the plane of vibration. The most notable variations in the absorbance levels were observed for the symmetric and asymmetric stretching modes of phosphodiester groups of cellular nucleic acids [57]. The overlapping between the absorption bands makes it difficult to determine band intensities accurately. A simple approach is to regard the spectra as a characteristic fingerprint of the conformational change. Therefore, conformational change in the spectrum may be used to recognize and define transient conformational states of a protein [46].
The absorption spectra revealed several noticeable changes in the amides (IV-VI) regions due to exposure to SMF, as summarized in table 1 and shown in the relevant figures. Most of these bands have shown an increase in the intensity due to exposure to the magnetic field, which implies an increase in the transition dipole moment for these absorption bands. The peak at 512 cm −1 has shown a slight increase in its intensity due to the SMF effect on the NH out-of-plane bending vibrations. The most substantial rise in intensities happened to the bands that involve CO out-of-plane bending with some out-of-plane displacement of the NH group at 595 and 612 cm −1 , respectively. A decrease in intensity occurred in the bands 632 cm −1 and 737 cm −1 due to the magnetic field effect on the CO in-plane bending, CC stretch, and CNC deformation [50].
Tau protein is classified as a natively unfolded protein, and it is expected to have a very low content of secondary structural elements [58,59]. Therefore, the absorption bands in the amide III region have shown relatively weaker bands compared to the other bands, as shown in figure 4. The band at 1430 cm −1 increased in intensity and shifted to 1427 cm −1 , while a new weak band seems to be awakened at 1441 cm −1 and the band at 1450 cm −1 showed a drop in its intensity after tau exposure to SMF.
The absorption bands in amide II and amide I were not affected by the tau exposure to SMF, where little or no changes were observed regarding both intensities and peak positions. The lack of changes can be connected to the low content of secondary structure elements or the small effect on the involved vibrational bonds. It is worth noting that the increase and decrease of intensities should correspond respectively to the peaks and the inverted peaks in the difference spectra in figure 6 and figure 7.
The absorption bands for the range (1700-4000) cm −1 are listed in table 2, where they have maintained their positions with little or no intensity increase after exposing tau protein to SMF. Only these bands 2340, 2358, 2829, 2850, 2872, 2917, 2934, and 2960 cm −1 have shown a noticeable significant increase in their intensities, out of which the bands at (2872 and 2960) cm −1 involve a symmetric and asymmetric stretch of the C-H methyl group, respectively. Also, the bands at (2917 and 2934) cm −1 involve the asymmetric stretch of the C-H methylene group, while the band at 2850 cm −1 involves the symmetric stretch of the C-H methylene group. These peaks are associated with the presence of saturated lipids, and any intensity increase, mainly CH 2 vibrations, can indicate higher content of saturated lipids. An increase in saturated lipids is related to vascular perturbations, which may lead to developing dementia [60][61][62].
The absorption bands at (2340 and 2358) cm −1 have shown a moderate increase in their intensities while maintaining their positions. This is also attributed to changes imposed by the magnetic field on molecular vibrations involving C-C or C-N triple bonds.
The increase in the intensity of the absorption bands because of tau protein exposure to SMF should be proportional to the square of the dipole moment magnitudes of those bands. The transition dipole moment matrix (R α,k in equation (3)) can increase in magnitude by increasing the charge of the dipole moment or the separating distance between the charges; otherwise, all other variables are constant. The exerted magnetic force can induce the above changes in the vibrating atoms of the active molecules.
Where q and v are the charge and velocity of the atoms of the active molecule, and θ is the angle between the force and velocity. The magnetic force can exert torque on molecular vibration to align the molecules in the direction of the magnetic field [63]. Moreover, the magnetic force may lead to changes in the amplitude of vibrations and therefore increase or decrease the intensity of the absorption band depending on the molecular orientations with respect to the magnetic field direction. The magnetic field imposes changes on the molecular structure of the protein in the form of aligning and twisting the molecular vibrations, therefore, affecting the bands' intensities. The magnetic force tends to affect asymmetric and out-of-plane motions more than symmetric and in-plane vibrations.
The absorbed molecular frequency may shift because of changes imposed by the magnetic force on molecular vibrations. In other words, any changes in the molecular environment may lead to changes in the spring constant or the displacement of the molecular vibrations affecting the absorbed energy of the molecule. Therefore, exposure of tau protein to SMF can cause changes in the absorbed energy of molecular vibrations and allow some bands to become susceptible to shifting their peak positions.
Our experimental results showed that tau protein exposure to SMF strongly influences the vibrations that involve C-O out-of-plane bending vibration with out-of-plane displacements of the NH group. One may speculate that the effect of the magnetic force on the bending vibrating atoms comes in the form of additional torque twisting the vibrating molecules. Therefore, enhancing the potential energy and kinetic energy of the moving atoms increases the frequency of vibration, and causes the shift in peak position and the increase in intensity.
In the case of amide B, the C-H stretching vibrations are the result of Fermi resonance of the amide II band, which means the frequency has been doubled while the stretching distance is half of that for the fundamental vibrational mode. The magnetic force acts on the vibrating atoms inducing a bending vibration to interfere with the stretching vibration. In other words, if a magnetic force is applied to a vibrating molecule, the magnetic force tends to align the molecules' vibration in its direction. The resulting torque induces an alternating bending effect on the vibrating molecules, which produces changes in the potential energy and the kinetic energy of the vibrating bonds. The magnetic force on moving charges in a magnetic field is expressed by equation (4) and is depicted in figure 8, which shows the induced magnetic forces on each moving charged atom.
The induced magnetic forces impose an out-of-plane bending on the stretched vibration. The resultant force has increased slightly during the stretching out and compressing in with a slight bend in the vibration direction. The increased forces in both directions of the vibrating molecule increase in the amplitude of vibration and yield an intensity increase.
The magnetic force is expected to be more effective against the lighter vibrating molecules such as CH 2 and CH 3 , which can be verified from equation (1), where the frequency ν 2 is proportional to K μ −1 . Meaning the ν 2 is proportional to the inverse of the reduced mass of the vibrating molecule. Besides, the induced magnetic force has a more proportional impact on vibrations with smaller vibrational amplitudes.
The experimental results have shown that tau protein is sensitive to SMF, reflected by intensity changes and shifts in peak positions at varying degrees for most absorption bands as listed in tables 1 and 2. Tau protein exposure to SMF resembles invoking a molecular environmental change leading to protein conformations through the vibrational changes and other magnetic interactions such as the surface tension generated by the magnetic pressure [64]. It seems that SMF induces molecular polarization in the exposed protein by aligning all molecular vibrations in the plane of the magnetic field direction. The magnetic force interferes by folding all normal protein functions into a two-dimensional surface. These momentary changes in the secondary and tertiary structures of the tau protein leave the possibility open for altering the shape of this sensitive microtubule protein and turning it into an insoluble misfolded protein. On the other hand, it is also possible to use SMF as a noninvasive technique to induce the needed changes to eliminate unwanted protein accumulations.
The intensities' decrease for some bands after the exposure to the magnetic field is caused by a suppressing effect on the amplitude of oscillation which modifies the molecular vibrations in these absorption bands. The inverted peaks in the difference spectra in figures 6 and 7 should also coincide with these bands' positions if there are no shifts. The same is true concerning the increase of intensities where the difference spectra peaks should correspond to the final frequency of the involved bands.
It seems once tau protein is exposed to SMF, a genuine interaction is induced, yielding changes in the protein's secondary and tertiary structures momentarily. The shifts in peak positions correlate to variations in the internal energy of the molecular structure of the protein, which may lead to instantaneous changes in the protein's structure. A magnetic field can affect molecular vibration and induce molecular distortion within the exposed protein. In other words, the magnetic field causes changes to the molecular environment; these induced changes can be helpful in some cases and harmful in others. For example, exposure to a certain strength of magnetic field leading to the unfolding of tau protein into a proper orientation could delay the progression of degenerative diseases. In contrast, exposure to a different type or strength of magnetic field could expedite the aggregation of tau protein and could facilitate the progression of such diseases. Besides, protein exposure to different strengths of magnetic fields and a wide range of electromagnetic radiation may reveal some clues behind protein misfolding or provide a biomarker measurement indicating some disease progression. Shows the vibrating molecule without being exposed to the magnetic field. (B) shows the molecule vibrations while being exposed to an inward magnetic field perpendicular to the plane of vibration. The green arrows indicate the direction of motion and represent the force on each atom and the blue arrows indicate the force direction on each atom by the magnetic field. The resultant force on the atoms increases with a little shift in each direction.
The importance of understanding the molecular mechanisms behind protein conformation stems from the need to understand these amyloid aggregates, known for their high heterogeneity and the increasing cases of neurotoxicity. Thus, brain pathogenesis leads to oligomer formations, which is the leading cause of most degenerative neurological diseases, where early detection using invasive techniques could be a lifesaver [37,[65][66][67][68]. FTIR spectroscopy is a simple technique to acquire spectra for comparison with a biomarker spectrum of the different neurological diseases to identify each disease. Brain exposure to TSMF can be used as a therapeutic procedure to alter protein conformations and dissolve amyloid oligomers [69]. However, such techniques require a complete understanding of the effects of magnetic fields on protein structure. Besides, more investigations are still needed to understand the mechanisms behind protein misfolding, fibril formation, and aggregation, which leads to most neurological diseases. In general, continued progress in FTIR spectroscopy and imaging, combined with other spectroscopic methods, can lead to an improved mastery, identification, and treatment of different protein-folding diseases [11].

Conclusion
The experimental results can be summarized: (1) Tau protein is susceptible to SMF exposure. A significant number of the absorption bands have shown changes in their intensities and peak positions. (2) The magnetic force can affect the molecular vibrations and twist these vibrations, affecting the tau protein's microtubule structure.
(3) The shifts in peak positions correspond to changes in the potential energy of the molecular vibrations; these changes are caused by the magnetic field forces on the vibrating atoms. A shift to higher potential energy implies an increase in the stretching amplitude or an increase in the protein force constant leading to a higher frequency in a more solidifying structure. (4) the variations of band intensities relate to the changes in the transition dipole moment or the rate of change for charge in the molecular dipole moment. (5) FTIR spectroscopy has the potential to be used as a sensor for early detections and classifications of dementia diseases through spectrum analysis of a single drop of plasmas. (6) SMF has the potential to be used as a spontaneous therapeutic procedure to impose changes on the molecular environment of the proteins.