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Tau protein is a major structural protein of the paired helical filaments (PHFs)found in both neuritic senile plaques and neurofibrillary tangles in Alzheimers'disease(AD).Senile plaques also contain amyloid B protein(AB). We did an immunochemical analysis of frontal cortex from 15 dialysis cases,5 Alzheimer's disease patients,and 6 control cases to see whether AD-like changes in Ab deposition and tau protein were linked to aluminum accumulation.Dialysis patients were used because they are frequently exposed to increased level of aluminum.8 of the 15 dialysis cases had insoluble AB,but there was no association between its presence and the accumulation of aluminum.However,we found AD-like changes in the processing of tau protein.In white matter,truncated tau protein in the PHF-core fraction and endogenously truncated tau in the supernatant fraction were both increased in association with aluminum accumulation in the brain.In grey matter,normal tau protein was depleted and insoluble hyperphosphorylated tau increased in association with the aluminium concentration.Protease-resistant PHFs were present in grey matter in 2 dialysis cases,a frequency above that expected for AD in this age group. PHF-core tau in both grey and white matter correlated with decreased levels of normal tau protein in white matter.These findings are consistent with a role for aluminum in the development of AD-like pathology in patients subjected to prolonged aluminum exposure. |
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