Aluminum in neurological disease - a 36 year multicenter study

Abstract

Aluminum is a ubiquitous neurotoxin highly enriched in our biosphere, and has been implicated in the etiology and pathology of multiple neurological diseases that involve inflammatory neural degeneration, behavioral impairment and cognitive decline. Over the last 36 years our group has analyzed the aluminum content of the temporal lobe neocortex of 511 high quality coded human brain samples from 18 diverse neurological and neurodegenerative disorders, including 2 groups of age-matched controls. Brodmann anatomical areas including the inferior, medial and superior temporal gyrus (A20-A22) were selected for analysis: (i) because of their essential functions in massive neural information processing operations including cognition and memory formation; and (ii) because subareas of these anatomical regions are unique to humans and are amongst the earliest areas affected by progressive neurodegenerative disorders such as Alzheimer's disease (AD). Coded brain tissue samples were analyzed using the analytical technique of: (i) Zeeman-type electrothermal atomic absorption spectrophotometry (ETAAS) combined with (ii) an experimental multi-elemental analysis using the advanced photon source (APS) ultra-bright storage ring-generated hard X-ray beam (7 GeV) and fluorescence raster scanning (XRFR) spectroscopy device at the Argonne National Laboratory, US Department of Energy, University of Chicago IL, USA. These data represent the largest study of aluminum concentration in the brains of human neurological and neurodegenerative disease ever undertaken. Neurological diseases examined were AD (N=186), ataxia Friedreich's type (AFT; N=6), amyotrophic lateral sclerosis (ALS; N=16), autism spectrum disorder (ASD; N=26), dialysis dementia syndrome (DDS; N=27), Down's syndrome (DS; trisomy21; N=24), Huntington's chorea (HC; N=15), multiple infarct dementia (MID; N=19), multiple sclerosis (MS; N=23), Parkinson's disease (PD; N=27), prion disease (PrD; N=11) including bovine spongiform encephalopathy (BSE; 'mad cow disease'), Creutzfeldt-Jakob disease (CJD) and Gerstmann-Straussler-Sheinker syndrome (GSS), progressive multifocal leukoencephalopathy (PML; N=11), progressive supranuclear palsy (PSP; N=24), schizophrenia (SCZ; N=21), a young control group (YCG; N=22) and an aged control group (ACG; N=53). Amongst these 18 common neurological conditions and controls we report a statistically significant trend for aluminum to be increased only in AD, DS and DDS compared to age- and gender-matched brains from the same anatomical region. The results continue to suggest that aluminum's association with AD, DDS and DS brain tissues may contribute to the neuropathology of these neurological diseases but appear not to be a significant factor in other common disorders of the human central nervous system (CNS).

Keywords: Aluminum; Alzheimer’s disease (AD); Dialysis dementia syndrome (DDS); Downs syndrome (DS; Trisomy 21); Electrothermal atomic absorption spectrophotometry (ETAAS); X-ray fluorescence raster (XRFR) scanning spectroscopy; neuropathology.