Elevated cerebral aluminum and early-onset Alzheimer's disease in an individual occupationally exposed to aluminum: a case report
Aluminum is a known neurotoxin and occupational exposure to aluminum has been implicated in neurological disease including Alzheimer's disease. Here we present the first complete and unequivocal data demonstrating the significantly elevated aluminum content of the brain in an individual occupationally exposed to aluminum.
A 66-year-old Caucasian male who died with Alzheimer's disease showed a significantly higher aluminum content in the brain, 2.98 (2.73) μg / g dry weight, n = 46, after occupational exposure to aluminum over a period of 8 years.
That the individual developed an aggressive form of early onset Alzheimer's disease suggests a role for aluminum in the etiology of the disease. That exposure to aluminum was through occupational exposure to aluminum dust suggests a prominent role for the olfactory system and lungs in the accumulation of aluminum in the brain.
Humans are experiencing increasing exposure to aluminum in everyday life . Aluminum accumulates in the brain with age  and exposure is associated with a number of neurodegenerative diseases . Occupational exposure to aluminum has been associated with neurodevelopmental effects [4, 5, 6], although there are very few data to describe the aluminum content in the brains of occupationally exposed individuals . Here are the first data demonstrating a significantly elevated brain aluminum content in an individual diagnosed with Alzheimer's disease following occupational exposure to aluminum.
In 2003, a 58-year-old Caucasian man with no previous medical history was diagnosed with Alzheimer's disease. Ten years before this he began work with the preparation of a new material (DARMATT KM1) used as insulation in the nuclear fuel and space industries. This work exposed him to aluminum sulfate "dust" daily for 8 years. An 'ordinary' dust mask was supplied to protect against inhalation of the materials. Shortly after starting this work he complained of headaches, tiredness and mouth ulcers. In 1999 he began to show problems with memory and suffered from depression. After his death, at age 66, in 2011, at the request of the family and the local coroner, samples of his brain tissue were sent to the John Radcliffe Hospital at Oxford University, UK, for clinical diagnosis and a frozen frontal lobe section. He was sent to Professor C Exley (Keele University, UK) for the determination of aluminium tissue. The clinical diagnosis reported an abundance of argyrophilic plaques β-amyloids and a profusion of neurofibrillary tangles in all areas of his cerebral cortex; neuropathology is consistent with the characteristics of advanced Alzheimer's disease.
The frontal lobe tissue (approximately 20 g frozen weight) was thawed and then divided into 50 portions of similar size, each weighing approximately 300 mg. These were placed in an incubator at 37ºC and allowed to reach a constant dry weight for approximately 72 hours (Table 1). The dry tissues were then digested using a 1:1 mixture of 15.8 M nitric acid and 30% p/V hydrogen peroxide in a microwave oven using established methods . All samples produced clear digests and the total aluminum in each sample was measured by atomic absorption spectrometry with transverse heated graphite furnace using established and fully verified methods . The aluminium contents of three tissue samples
(IDs 6, 8 and 9) were below the value of the blank method and were recorded as zero for statistical purposes. The dry weights of three tissue samples (ID 2, 14 and 18) were less than 10 mg and the aluminum contents of these samples were also excluded from statistical analyses because such very low dry weights can disproportionately influence the final aluminum content. The average aluminium content of the remaining tissues (n = 46) was 2.98 with a standard deviation of 2.73 g / g dry weight and an interval of 0.00 to 12.97 g / g dry weight.
It is extremely rare that 20 g of brain tissue can be tested for elemental analysis. This opportunity allowed for the most complete analysis of the aluminum content of a single region of an individual's brain. The data are revealing with respect to the wide range of aluminum contents recorded, confirming the alleged focal accumulation of aluminum in human brain tissue, and with respect to an average value of 46 samples, 2.98 μg / g dry weight, which is more than three times greater than an average value, 0.83 μg / g dry weight, previously recorded for multiple frontal lobe samples from multiple individuals . Excluding the three very high values (IDs 2, 14 and 18) 30% of the measured aluminum contents were greater than 3.50 μg / g dry weight and could be considered potentially pathological [3, 8]. The opportunity to analyze up to 50 different tissue samples from a region of the brain has provided unequivocal evidence of excessive aluminum loading in the frontal lobe of an individual who was professionally exposed to aluminum over a period of 8 years. The clinical diagnosis of early-onset sporadic Alzheimer's disease showing post mortem characteristics of advanced disease at age 66 is suggestive of the aggressive etiology of the disease and the likely involvement of aluminum in the onset and progression of the disease. The high aluminum content in the brain tissue was similarly implicated in a recent case of congophilic ambolytic angiopathy in which the onset of the disease was again very early and the post mortem pathology was very advanced in an individual at the end of 50 years. While it is impossible to know whether high levels of cerebral aluminum cause disease in any of these cases, it is very likely, considering the known neurotoxicity of aluminum, that aluminum contributes to the aetiology of the disease, which could result in earlier onset and faster progression of a nascent condition.
Christopher ExleyEmail author and Thomas Vickers
Journal of Medical Case Reports20148: 41
DOI: 10.1186 / 1752-1947-8-41 © Exley and Vickers; Licensee BioMed Central Ltd. 2014
Received: December 4, 2013 Accepted: January 16, 2014 May: February 10, 2014