Aluminium in Brain Tissue in Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a devastating and debilitating neurodegenerative disease of unknown cause. A consensus suggests the involvement of both genetic and environmental factors of which the latter may involve human exposure to aluminium. There are no data on the content and distribution of aluminium in human brain tissue in MS. The aluminium content of brain tissue from 14 donors with a diagnosis of MS was determined by transversely heated graphite furnace atomic absorption spectrometry. The location of aluminium in the brain tissue of two donors was investigated by aluminium-specific fluorescence microscopy. The aluminium content of brain tissue in MS was universally high with many tissues bearing concentrations in excess of 10 μg/g dry wt. (10 ppm) and some exceeding 50 ppm. There were no statistically significant relationships between brain lobes, donor age or donor gender. Aluminium-specific fluorescence successfully identified aluminium in brain tissue in both intracellular and extracellular locations. The association of aluminium with corpora amylacea suggests a role for aluminium in neurodegeneration in MS.

Aluminium in Brain Tissue in Non-neurodegenerative/Non-neurodevelopmental Disease: A Comparison with Multiple Sclerosis

“…Random effects show the veffects of the nested and unbalanced factors: donor, lobe and sample. The marginal R 2 considers only the variance of the fixed effects, while the conditional R 2 takes both the fixed and random effects into account CI confidence interval, df degrees of freedom (Mold et al 2018b). While it confirmed a previous observation of age as a risk factor for brain aluminium content in a non-neurologically affected population (Roider and Drasch 1999), it also suggests that a correlation with age may not be significant in neurologically impaired populations.…”

“…Detailed statistical analyses showed unequivocally that the content of aluminium in brain tissue in MS was significantly higher than that in non-MS control group. This is the first unequivocal confirmation that aluminium is increased in brain tissue in MS (Mold et al 2018b) and it further supports the contention that the body burden of aluminium is elevated in MS compared to individuals without MS (Exley et al 2006;Jones et al 2017). The data do not prove a role for aluminium in MS, but a higher content of a neurotoxin and powerful pro-oxidant (Verstraeten et al 1997;Exley 2004) in brain tissue in MS cannot be discarded as a putative aetiological factor in a disease with both genetic and environmental components (Thompson 2017).…”

“…There are no other confirmed risk factors for the accumulation of aluminium in brain tissue though aluminium is shown to be elevated in a number of neurodegenerative and neurodevelopmental disorders including familial Alzheimer's disease (fAD) (Mirza et al 2017) and autism spectrum disorder (ASD) (Mold et al 2018a). Recently, we made the first analyses of aluminium in brain tissue in individuals who died with a diagnosis of the neurological condition, multiple sclerosis (MS) (Mold et al 2018b). Our previous research had suggested that individuals with MS had a higher-than-expected body burden of aluminium (Exley et al 2006;Jones et al 2017) and this prompted us to look for aluminium in MS brain tissue.…”

Aluminium in human brain tissue from donors without neurodegenerative disease: A comparison with Alzheimer’s disease, multiple sclerosis and autism

“…www.nature.com/scientificreports www.nature.com/scientificreports/ When we compared the new control data set with data produced in an identical manner in donors dying with diagnoses of sporadic Alzheimer's disease (sAD) 16 , familial Alzheimer's disease (fAD) 11 , autism spectrum disorder (ASD) 13 and multiple sclerosis (MS) 12 all of these disease groups had significantly higher brain aluminium content. The differences were always highly significant regardless of the method of statistical analysis (Table 4).…”

“…While there is no longer any debate as to the presence of aluminium in human brain tissue, there remains the question of how much aluminium in brain tissue is too much 10 . A number of recent studies have provided data on aluminium content in brain tissue in Alzheimer's disease 11 , multiple sclerosis 12 and autism 13 . The quantitative data, supported by aluminium-specific imaging, are invariably reported as being high, higher than expected.…”