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Metals and the amyloid cascade hypothesis of Alzheimer’s disease
New research could explain why some people with senile plaques do not suffer from dementia.
The study, led by Professor Christopher Exley, of The Birchall Centre at Keele University, and Professor Margaret Esiri, at John Radcliffe Hospital, Oxford, suggests that a high brain tissue ratio of copper to aluminium protects against neurotoxicity associated with the deposition of amyloid-b and the amyloid cascade hypothesis.
Aluminium, iron and copper are all implicated in the factors that cause neurodegenerative diseases. However, there is no consensus as to their direct involvement in Alzheimer’s disease or, indeed, whether they are elevated or not in the brain in Alzheimer’s disease.
While senile plaques composed of amyloid-b1-42 are one of the pathological hallmarks of the Alzheimer’s disease brain it is also the case that apparently identical structures are found in aged brains from donors with no Alzheimer’s disease. These observations question the role for amyloid-b and the amyloid cascade hypothesis in the factors that cause Alzheimer’s disease.
The study on 60 aged human brains identified a number of relationships between the degree of severity of amyloid-b neuropathology and the metal content of tissue from the donor brains. The latter was recently published for aluminium, copper and iron (House et al. (2012) Metallomics 4, 56-65).
Specifically, the extent and severity of amyloid-b deposition was inversely related to the copper content of brain tissue. Lower copper resulted in more severe and more extensive deposition of amyloid-b in the donor brain.
Further analyses of data for amyloid-b deposition and metal content raised an additional relationship between the ratio of copper to aluminium in brain tissue to the diagnosis of dementia. The research suggested that for those individuals with moderate to severe amyloid pathology, a copper to aluminium ratio of less than 20 predicted dementia.
Professor Exley said: “The hypothesis requires further testing but if proven correct it could explain why some individuals with senile plaques do not suffer from dementia. The implication being that a high brain tissue ratio of copper to aluminium protects against neurotoxicity associated with the deposition of amyloid-b and the amyloid cascade hypothesis.”
This research will be published in a forthcoming issue of the Journal of Alzheimer’s Disease
Enquiries to Professor C Exley, The Birchall Centre, Lennard-Jones Laboratories, Keele University, Staffordshire, UK. firstname.lastname@example.org