Abstract
The presence of magnetic nanoparticles (MNPs) in the human brain was attributed until recently to endogenous formation; associated with a putative navigational sense, or with pathological mishandling of brain iron within senile plaques. Conversely, an exogenous, high-temperature source of brain MNPs has been newly identified, based on their variable sizes/concentrations, rounded shapes/surface crystallites, and co-association with non-physiological metals (e.g., platinum, cobalt). Here, we examined the concentration and regional distribution of brain magnetite/maghemite, by magnetic remanence measurements of 147 samples of fresh/frozen tissues, from Alzheimer’s disease (AD) and pathologically-unremarkable brains (80–98 years at death) from the Manchester Brain Bank (MBB), UK. The magnetite/maghemite concentrations varied between individual cases, and different brain regions, with no significant difference between the AD and non-AD cases. Similarly, all the elderly MBB brains contain varying concentrations of non-physiological metals (e.g. lead, cerium), suggesting universal incursion of environmentally-sourced particles, likely across the geriatric blood–brain barrier (BBB). Cerebellar Manchester samples contained significantly lower (~ 9×) ferrimagnetic content compared with those from a young (29 years ave.), neurologically-damaged Mexico City cohort. Investigation of younger, variably-exposed cohorts, prior to loss of BBB integrity, seems essential to understand early brain impacts of exposure to exogenous magnetite/maghemite and other metal-rich pollution particles.
Highlights
The presence of magnetic nanoparticles (MNPs) in the human brain was attributed until recently to endogenous formation; associated with a putative navigational sense, or with pathological mishandling of brain iron within senile plaques
Mass-normalized SIRMs of the Manchester brain samples ranged from 0.06 to 13.69 × 1 0−6 Am2 kg−1, equating to between ~ 4 and 992 ng of magnetite g −1 tissue and median of 0.44 × 1 09 MNPs g−1 (or between ~ 5 and 1140 ng of maghemite g−1 tissue and median of 0.53 x 1 09 MNPs g −1 (Table 1, Figure 2). These SIRM values are on average ~11× higher than those reported for formaldehyde-stored brains[47]. They are similar in magnitude (Supplementary Fig. S4) to those obtained for fresh/frozen brain samples, from the medial temporal g yrus[50] (SIRMs measured at temperatures below 293 K e.g. at 77 K or 100 K, are often higher, as they capture the additional remanence of magnetic particles so small (< ~ 30 nm) as to be magnetically unstable at room temperature)
Using superconducting quantum interference device (SQUID) magnetometry on fresh-frozen human tissue samples, we find a heterogenous distribution of magnetite/maghemite across the brain regions sampled from Alzheimer’s disease (AD) and control cases from northern England
Summary
The presence of magnetic nanoparticles (MNPs) in the human brain was attributed until recently to endogenous formation; associated with a putative navigational sense, or with pathological mishandling of brain iron within senile plaques. Iron participates in biochemical reactions, such as the generation of ATP in mitochondria and transport of oxygen via haemoglobin, but is a crucial part of brain-specific functions such as axon m yelination[1] and synthesis of various neurotransmitters, like dopamine[2]. This versatility comes at a price; the ease of valence change can have detrimental effects if, for example, free (unbound) iron becomes available to react with oxygen and produce damaging free radicals. Interruptions to this process may be pathological; reduced iron capacity of transferrin[16], impaired functioning of ferritin[17] or decreased expression of ferritin[18] are all proposed mechanisms for the iron accumulation observed in NDD19
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