Alzheimer's-disease-like changes in tau protein processing: association with aluminium accumulation in brains of renal dialysis patients.
Tau protein is a major structural protein of the paired helical filaments (PHFs) found in both neuritic senile plaques and neurofibrillary tangles in Alzheimer's disease (AD). Senile plaques also contain amyloid beta protein (A beta). 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 A beta deposition and tau protein were linked to aluminium accumulation. Dialysis patients were used because they are frequently exposed to increased levels of aluminium. 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 endogenously truncated tau in the supernatant fraction were both increased in association with aluminium accumulation in the brain. In grey matter, normal tau protein was depleted and insoluble hyperphosphorylated tau increased in association with 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 aluminium in the development of AD-like pathology in patients subjected to prolonged aluminium exposure.
Harrington
C R
CR
Cambridge Brain Bank Laboratory, University Department of Psychiatry, Medical Research Council Centre, UK.
Wischik
C M
CM
McArthur
F K
FK
Taylor
G A
GA
Edwardson
J A
JA
Candy
J M
JM
D000328:Adult; D000368:Aged; D000535:Aluminum / Q000097:blood / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D016875:tau Proteins / Q000378:metabolism*
D016875:tau Proteins; D000535:Aluminum