Single-domain magnetic particles with motion behavior under electromagnetic AC and DC fields are a fatal cargo in Metropolitan Mexico City pediatric and young adult early Alzheimer, Parkinson, frontotemporal lobar degeneration and amyotrophic lateral sclerosis and in ALS patients

Abstract

Metropolitan Mexico City (MMC) children and young adults exhibit overlapping Alzheimer and Parkinsons' diseases (AD, PD) and TAR DNA-binding protein 43 pathology with magnetic ultrafine particulate matter (UFPM) and industrial nanoparticles (NPs). We studied magnetophoresis, electron microscopy and energy-dispersive X-ray spectrometry in 203 brain samples from 14 children, 27 adults, and 27 ALS cases/controls. Saturation isothermal remanent magnetization (SIRM), capturing magnetically unstable FeNPs ~ 20nm, was higher in caudate, thalamus, hippocampus, putamen, and motor regions with subcortical vs. cortical higher SIRM in MMC ≤ 40y. Motion behavior was associated with magnetic exposures 25-100 mT and children exhibited IRM saturated curves at 50-300 mT associated to change in NPs position and/or orientation in situ. Targeted magnetic profiles moving under AC/AD magnetic fields could distinguish ALS vs. controls. Motor neuron magnetic NPs accumulation potentially interferes with action potentials, ion channels, nuclear pores and enhances the membrane insertion process when coated with lipopolysaccharides. TEM and EDX showed 7-20 nm NP Fe, Ti, Co, Ni, V, Hg, W, Al, Zn, Ag, Si, S, Br, Ce, La, and Pr in abnormal neural and vascular organelles. Brain accumulation of magnetic unstable particles start in childhood and cytotoxic, hyperthermia, free radical formation, and NPs motion associated to 30-50 μT (DC magnetic fields) are critical given ubiquitous electric and magnetic fields exposures could induce motion behavior and neural damage. Magnetic UFPM/NPs are a fatal brain cargo in children's brains, and a preventable AD, PD, FTLD, ALS environmental threat. Billions of people are at risk. We are clearly poisoning ourselves.

Keywords: Alzheimer; Motion nanoparticle behavior; Parkinson; brain magnetic nanoparticles; frontotemporal lobar degeneration; pediatric Alzheimer; saturation isothermal remanent magnetization SIRM; single domain FeNPs.

Figure 1

Saturation isothermal remanent magnetization SIRM values were obtained from dust urban road samples in MMC in March 2017. Darker blue color indicates areas with high concentration of magnetic minerals (ferrimagnetic). A highly populated area in MMC Iztapalapa (~2 million people) is a prime example of high ferrimagnetic materials.

Figure 2

Trend of annual averaged over 3 years box plots of mean 24-h PM_2.5 for five representative MMC monitoring stations from 1989 to 2023. COVID period information is not available. The red triangles represent the annual mean and the red line the current PM_2.5 annual US EPA NAAQS (9 μg/m³). Box plots from the years before 2004 were estimated from available information of PM₁₀ 24-h averages since 1989 and the mean slope of the correlation PM₁₀ vs. PM_2.5 between 2004 and 2007. Data from: http://www.aire.cdmx.gob.mx/default.php#.

Figure 3

Trends of estimated particle number concentrations (PNCs)-a calculated estimation of nanoparticles- and the associated annual medians of 1-h average Carbon monoxide (CO) for five representative monitoring stations of the MMC from 1989 to 2023. The colored circles in the figure correspond to the medians of PNCs measured by the authors referenced in Aguilar-Castillo (2023), Velasco et al. (2019), Caudillo et al. (2020), Dunn et al. (2004), and Kleinman et al. (2009). CO data source: http://www.aire.cdmx.gob.mx/default.php#.

Figure 4

Curves of ARM obtained in an AC field of 100 mT and DC field of 30, 40, and 50 μT and equal-angle projection of magnetization direction of brain samples.

Figure 5

Distribution of highly magnetic particles in the 203 brain samples, including cortical and subcortical regions. Please notice children and young adults exhibit high magnetic particle concentrations.

Figure 6

IRM₁₀₀₀ (SIRM) measurements in subcortical vs. cortical regions in individuals younger than 40y of age, p = 0.0234 higher in subcortical regions.

Figure 7

IRM acquisition curves from different brain anatomical areas in males ages 11 months to 24 years. The gray area indicates the mT intensity field at which the ferromagnetic minerals reached IRM saturation values (i.e., magnetization of saturation).

Figure 8

Equi-angular projection diagrams of magnetic vector components of different brain regions in an 11-month-old (A) and subjects ages 3, 14, 16, and 24 years (B). T1, T2, and T3 magnetic behavior is correlated with the displacement of magnetic particles, i.e., x in direction to 0 degrees, −x in direction to 180 grades.

Figure 9

Sensory and Motor areas and T3 behavior in relationship with the MRI acquisition for the targeted region.

Figure 10

Single domain ≤ 15 nm Fe Br and Si particles in caudate head samples. FeBr₂ exhibits a strong metamagnetism at 4.2 K and it is a prototypical metamagnetic compound.

Figure 11

Caudate head sample from a 3y old boy (CO18) displays a combination of Al, Ti, Fe, along Si, S, Ca, and Cl. Oxygen is the major component with 63%.

Figure 12

Thalamus from a 16y old boy (CO 43) with a T3 behavior and a high SIRM (Figure 9). Vanadium, titanium and iron were the predominant metals.

Figure 13

Medulla from 68y old male ALS control (CO65) exhibits a combination of oxidized Cu, Fe, Al, Si, and Ca.

Figure 14

Neurovascular unit pathology in exposed MMC young residents. (A) Substantia nigra neurovascular unit with significant perivascular neuropil vacuolization (*), with loss of astrocytic feet to the capillary wall and axonal changes in the vicinity of the blood vessel. A red blood cell is seen in the vessel lumen, in close contact with the endothelial surface. (B) Midbrain capillary showing an extensive perivascular neuropil vacuolization damage (*) associated with the accumulation of lipid vacuoles (+) in the proximity of the vessel. (C) High magnification of a tight junction cell–cell adhesion complex, between two endothelial cells showing the NPs deposition within the TJ structure (arrow). NPs are also present in the EC cytoplasm and mitochondria (m). (D) Olfactory bulb capillary with a luminal RBC loaded with NPs, also present in the EC cytoplasm. An RBC fragment is already within the endothelial cell. (E) Seventeen-year-old C087 frontal cortex showing a capillary with a luminal RBC already fragmented and one such RBC fragment already inside the EC (open arrows). (F) Cerebellar vermis in the 17y old from (E), the luminal RBC is in close contact with the EC (arrows) and NPs are being transferred inside the endothelium. (G) Gray matter cervical spinal cord CO24 toddler showing the activated EC with numerous filopodia (arrows) reaching the RBC surface. A few EC filopodia fragments are free in the lumen. The NVU is an early targeted structure in UFPM/NPs exposures.

Figure 15

Electron micrographs of NPs in diverse organelles. (A) A classical magnetite spherical anthropogenic particle (arrow) is identified in a caudate head neuron, in close proximity to the nucleus. (B) Vagus nerve section showing a longitudinally cut axon with two spherical magnetite nanoparticles (arrows). Notice adjacent transverse axons with vacuolated myelin sheets (*). (C) Same vagal nerve with a double membrane axonal structure (arrows) showing numerous nanoparticles in the range of 5 nm. The structure could be a mitochondria with no intact cristae. (D) A close-up of a vacuolated (*) axonal myelin sheet showing an spherical NPs (arrow). (E) Cerebellar vermis with a longitudinally cut axon showing three mitochondria with matrix NPs (arrows). Notice the myelin sheet split (*). (F) Caudate neuronal autophagosomes with different stages; abnormal mitochondria (short arrows) are seen along the lysosome fusion and degradation of compartments (open arrows). (G) Substantia nigrae dilated endoplasmic reticulum (ER) is identified along mitochondria with NPs (short arrow) and a mitochondria in close contact with neuromelanin containing NPs (open arrows).

Figure 16

Immunohistochemistry in young MMC residents with hallmarks of AD, PD, and TDP-43 pathology. (A) Temporal cortex in a teen residing in an area with high dust SIRM. Amyloid plaques are numerous (brown product) and extend throughout the cortex. The subarachnoid space is marked (*). (B) The same child, with numerous Hirano bodies in temporal neurons. Insert shows a ghost neuron with a tangle. (C) Thirty-five year old C108 frontal amyloid plaque (red product short arrows) and a reactive astrocyte GFAP+ (black thick arrow). (Da,Db) young adults showing p-Tau in frontal neurons and overlapping with TDP-43 pathology: positive frontal nuclear neurons (long arrow) and negative neurons (short arrow). (E) This 14y old C125 had frontal p-Tau plaques (arrows, brown product), same child as Da. (F) Third cranial nerve nucleus TDP-43 positive nuclear staining (short arrow) contrast with the lack of nuclear staining in adjacent neurons (long arrow). (G) This 3y old CO16 displays coiled tangles in oligodendroglia cells stained with TDP-43 (short arrow, brown product), please notice the nuclear depletion of TDP-43 immunostaining. (H) Same child as (A), olfactory bulb glomerular region stained with alpha synuclein, red positive staining (arrows). (I) Substantia nigra Lewy bodies C145 in a 31y old. (J) Frontal cortex C170 with numerous abnormal white matter dendrites and axons positive for abnormal intermediate neurofilaments. (K1,K2) Olfactory nucleus in the olfactory bulb and the dentate gyrus in the hippocampus showing strongly stained p-Tau nuclei versus negative nuclei, a common finding in MMC children. (L) Olfactory bulb p-Tau plaque (arrows, brown product).