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 disease (AD). Brains taken at autopsy (n = 50) from patients with a history of long-term hemodialysis (HD) and intake of aluminium (Al)-containing drugs were examined by light microscopy. Using our modified silver stain we have been able to demonstrate and clearly discriminate between AD changes and dialysis-associated encephalopathy (DAE) on paraffin sections; evaluation was done with a 3-point scale. DAE morphology is characterized by lysosome-derived intracytoplasmic, Al-containing, pathognomonic, argyrophilic inclusions in choroid plexus epithelia, cortical glia and neurons. A statistically significant difference was found between the amounts of drug-related Al ingested and the degree of DAE-related morphological change (P < 0.001). On the other 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 A4 amyloid (beta A4) and/or a low incidence of AD-type neurofibrillary tangles (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, isolated cases from a group of 127 long-term hemodialyzed patients have been reported previously, who presented with intermingled, clearly distinguishable lesions of both age-related AD morphology and DAE changes. Comparison of AD morphology with an age-matched control group was not statistically significant (P > 0.6 for beta A4, P > 0.7 for NFT). In our experience, Al does not cause an increase in AD morphology, at least not in terms of bioavailable Al in drugs or as a result of long-term HD.
Reusche
E
E
Institute of Pathology/Neuropathology, Medical University Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. reusche@patho.mu-luebeck.de
Koch
V
V
Lindner
B
B
Harrison
A P
AP
Friedrich
H J
HJ
D000328:Adult; D000368:Aged; D000375:Aging / Q000473:pathology; D017607:Aluminum Compounds / Q000633:toxicity*; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D006435:Renal Dialysis / Q000009:adverse effects*; D016622:Silver Staining; D016875:tau Proteins / Q000378:metabolism
D017607:Aluminum Compounds; D016564:Amyloid beta-Protein Precursor; D016875:tau Proteins