ALZHEIMERS-DISEASE-LIKE CHANGES IN TAN PROTEIN PROCESSING - ASSOCIATION WITH ALUMINUM ACCUMULATION IN BRAINS OF RENAL DIALYSIS PATIENTS

Tau protein is a major structural protein of the paired helical filame nts (PHFs) found in both neuritic senile plaques and neurofibrillary t angles in Alzheimer's disease (AD). Senile plaques also contain amyloi d beta protein (A beta). We did an immunochemical analysis of frontal cortex from 15 dialysis cases, 5 Alzheimer's disease patients, and 6 c ontrol cases to see whether AD-like changes in A beta deposition and t au protein were linked to aluminium accumulation. Dialysis patients we re used because they are frequently exposed to increased levels of alu minium. 8 of the 15 dialysis cases had insoluble A beta, but there was no association between its presence and the accumulation of aluminium . However, we found AD-like changes in the processing of tau protein. In white matter, truncated tau protein in the PHF-core fraction and en dogenously truncated tau in the supernatant fraction were both increas ed in association with aluminium accumulation in the brain. In grey ma tter, normal tau protein was depleted and insoluble hyperphosphorylate d tau increased in association with aluminium concentration. Protease- resistant PHFs were present in grey matter in 2 dialysis cases, a freq uency above that expected for AD in this age group. PHF-core tau in bo th grey and white matter correlated with decreased levels of normal ta u protein in white matter. These findings are consistent with a role f or aluminium in the development of AD-like pathology in patients subje cted to prolonged aluminium exposure.