The Contribution of Aluminium to Alzheimer’s disease: A Neuropathological Investigation of Renal Dialysis Cases

Whilst controversial, the role of aluminium in Alzheimer's disease (AD) has not been adequately explained as models of aluminium exposure are not generally available. Renal dialysis (RD) patients are exposed to aluminium through phosphate-binding compounds for controlling hypophosphatemia and because of impaired renal excretion accumulate aluminium in tissues including the brain.These individuals represent a suitable population to study the role of aluminium exposure in inducing AD changes in the brain.We studied the brains of 28 RD individuals, with a history of haemodialysis or peritoneal dialysis, for the presence of AD-type changes and glial pathology, and related these to aluminium exposure and to Apolipoprotein E (APOE) genotype. RD patients had increased Aβ deposition compared to controls but this did not relate to brain aluminium. RD cases carrying the APOEε4 allele were more likely to show Aβ deposition, though cases not carrying the APOEε4 allele also showed Aβ deposition. Neurones immunostaining with AT8 against a phosphorylated epitope of Tau were identified in RD brains though neurofibrillary tangles were not observed. A slight increase in the numbers of microglia was also identified in the brains of RD cases compared to controls. Whilst neuropathological changes suggestive of early AD-type pathology associate with RD, they could not be attributed to aluminium exposure but may be related to the presence of the APOEε4 allele acting in conjunction with other RD pathological processes. Aluminium therefore does not appear to be a major risk factor contributing to AD