Aluminium accumulation in relation to senile plaque and neurofibrillary tangle formation in the brains of patients with renal failure

• Published in: Journal of the neurological sciences Vol. 107; no. 2; pp. 210 - 218
• Main Authors: Candy, J.M., McArthur, F.K., Oakley, A.E., Taylor, G.A., Chen, C.P.L.-H., Mountfort, S.A., Thompson, J.E., Chalker, P.R., Bishop, H.E., Beyreuther, K., Perry, G., Ward, M.K., Martyn, C.N., Edwardson, J.A.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01.02.1992; Elsevier Science
• Subjects: [formula omitted] Amyloid protein; Aluminium; Aluminum - analysis; Aluminum - metabolism; Aluminum - toxicity; Amyloid beta-Peptides - analysis; Amyloid beta-Protein Precursor - analysis; Antibodies, Monoclonal; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Brain - pathology; Female; Human brain; Humans; Immunocytochemistry; Immunohistochemistry; Kidney Failure, Chronic - metabolism; Kidney Failure, Chronic - pathology; Kidney Failure, Chronic - therapy; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Neurofibrillary tangle; Neurofibrillary Tangles - ultrastructure; Peritoneal Dialysis - adverse effects; Reference Values; Renal dialysis; Renal Dialysis - adverse effects; Renal failure; Retrospective Studies; Secondary ion mass spectrometry; Senile plaque; Immunocytochemistry; Senile plaque; Human brain; Renal dialysis; Secondary ion mass spectrometry; Aluminium; Neurofibrillary tangle; β A4 Amyloid protein; Human; Nervous system diseases; Urinary system disease; Senile plate; Exploration; Pathology; Chronic; Renal failure; Dialysis; Brain (vertebrata)
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/0022-510X(92)90291-R

The effects of long-term exposure to aluminium on the development of Alzheimer-type neuropathological changes have been studied post-mortem in patients with chronic renal failure who did not have dialysis encephalopathy. Administration of aluminium-containing phosphate binding compounds appears to be a major factor in the accumulation of aluminium in the brain of dialysis patients. The mean serum aluminium concentrations determined during life and brain aluminium concentrations determined post-mortem correlated with both the duration and total amount of aluminium hydroxide administered to these patients. No correlation was found between the presence of bone aluminium and either the mean serum or brain aluminium concentration. Longitudinal monitoring of serum aluminium concentrations may provide a more reliable index than bone biopsy of brain aluminium concentrations in dialysis patients. Dynamic secondary ion mass spectrometry revealed focal accumulations of aluminium associated with cortical pyramidal neurones. The majority of patients also showed immunostaining in pyramidal neurones with an antibody to the N-terminal region of the β A4 amyloid precursor protein, while staining was absent in age-matched control cases. One-third of the patients exhibited β A4- positive amorphous senile plaques in the cerebral cortex. However, there was no clear correlation between either the presence and intensity of β A4 amyloid precursor immunostaining or the presence of senile plaques and the concentration of aluminium in the cerebral cortex. Cortical neurofibrillary tangles were not observed in any of the dialysis patients. These data suggest that it is unlikely that aluminium plays any major role in neurofibrillary tangle formation and that its putative role in senile plaque formation is likely to be only part of a complex cascade of changes.