Alzheimer morphology is not increased in dialysis-associated encephalopathy and long-term hemodialysis

This study examines the role of aluminium in the etiology of Alzheimer's di sease (AD). Brains taken at autopsy (n=50) from patients with a history of long-term hemodialysis (HD) and intake of aluminium (Al)-containing drugs w ere examined by light microscopy. Using our modified silver stain we have b een able to demonstrate and clearly discriminate between AD changes and dia lysis-associated encephalopathy (DAE) on paraffin sections; evaluation was done with a 3-point scale. DAE morphology is characterized by lysosome-deri ved intracytoplasmic, Al-containing, pathognomonic, argyrophilic inclusions in choroid plexus epithelia, cortical glia and neurons. A statistically si gnificant difference was found between the amounts of drug-related Al inges ted and the degree of DAE-related morphological change (P<0.001). On the ot her hand no apparent microscopical increase in AD morphology was found. No AD changes were seen whatsoever in patients under the age of 60, despite a history of long-term HD with ingestion of "pure" Al up to 2.5 kg. Patients over 60 years of age occasionally presented with sparse deposits of <beta>A 4 amyloid (beta A4) and/or a low incidence of AD-type neurofibrillary tangl es (NFT). In accordance with CERAD criteria these were identified as normal , age-related phenomena (P<0.001 for <beta>A4; P<0.001 for NFT). Rare, isol ated cases from a group of 127 long-term hemodialyzed patients have been re ported previously, who presented with intermingled, clearly distinguishable lesions of both age-related AD morphology and DAE changes. Comparison of A D morphology with an age-matched control group was not statistically signif icant (P>0.6 for beta A4, P>0.7 for NFT). In our experience, Al does not ca use an increase in AD morphology, at least not in terms of bioavailable Al in drugs or as a result of long-term HD.