Researchers have found large deposits of aluminum and amyloid-beta — the protein that forms toxic aggregates in the brain and is thought to be involved in the onset of Alzheimer’s disease — in the same brain regions of patients with familial Alzheimer’s.
Their findings point towards a close relationship between brain aluminum content and the levels of amyloid-beta, possibly modulated by genetic factors that predispose individuals to the disease.
The research was published in a study, “Aluminum and Amyloid-β in Familial Alzheimer’s Disease,” in the Journal of Alzheimer’s Disease.
For more than 40 years, studies have suggested that aluminum and amyloid-beta are associated with each. Both are considered major risk factors for Alzheimer’s.
In a previous study, the same group of researchers discovered large amounts of aluminum in the brain of patients with familial Alzheimer’s, an inherited form of the disease caused by mutations in certain genes.
To investigate the possible relationship between aluminum and amyloid-beta, these investigators, from Keele University in collaboration with colleagues at University of Innsbruck, analyzed brain tissue samples from a group of Colombian donors with familial Alzheimer’s.
All patient donors carried the PS1-E280Aa mutation, which stimulates the production of amyloid-beta in the brain, leading to a rapid and severe progression of Alzheimer’s.
The researchers measured and compared the levels of aluminum in brain samples of patient donors to those of individuals who did not have any neurological or neurodegenerative disorder (controls).
To examine where aluminum was accumulating in the brain, they used aluminum-specific fluorescence microscopy imaging — a powerful microscopy technique that uses fluorescent lasers to detect aluminum in the brain. The same microscopy technique was used to assess if aluminum deposits were present in the same regions where amyloid-beta was found.
In nearly half of the patient samples (42%), the levels of aluminum were found to be higher than 3.00 μg/g dry weight, which is considered “pathologically significant,” or likely to contribute to disease progression and severity.
In addition, the median levels of brain aluminum were significantly higher among those with familial Alzheimer’s compared to controls (2.19 versus 0.60 μg/g dry weight).
Microscopy findings revealed that aluminum and amyloid-beta were mostly found in senile plaques scattered across different parts of the brain and, to a lesser extent, in blood vessels. Of note, senile plaques are deposits of amyloid-beta that form in patients with Alzheimer’s, and also as a consequence of normal aging.
“This is the second study confirming significantly high brain accumulation in familial Alzheimer’s disease, but it is the first to demonstrate an unequivocal association between the location of aluminum and amyloid-beta in the disease. It shows that aluminum and amyloid-beta are intimately woven in the neuropathology,” Christopher Exley, PhD, professor at Keele University and senior author of the study, said in a press release.
The researchers also found aluminum inside axons — extensions of neurons responsible for the transmission of electrical signals — and glia, a type of nerve cell that supports and protects neurons.
According to the authors, the aluminum found inside axons may be associated with tau, another protein that is thought to cause, or at least contribute to, the development of Alzheimer’s, but this is yet to be confirmed.
The study’s findings suggest that genetic mutations associated with familial Alzheimer’s may promote aluminum buildup in the brain, which then leads to the accumulation of amyloid-beta in the same region, or vice-versa.
“One could envisage increased amyloid-beta in brain tissue as a response to high levels of aluminum content, or that aluminum fosters the accumulation of amyloid-beta,” Exley said.
“Either way, the new research confirms my resolve that within the normal lifespan of humans, there would not be any AD [Alzheimer’s disease] if there were no aluminum in the brain tissue,” he added. “No aluminum, no AD.”
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