Argyrophilic inclusions distinct from Alzheimer neurofibrillary changes in one case of dialysis-associated encephalopathy

Abstract

A 72-year-old female demonstrated neurofibrillary changes of Alzheimer's disease (AD) as well as morphological features of dialysis-associated encephalopathy (DAE). This unique autopsy case was selected from a group of 127 patients with a history of long-term hemodialysis. Silver-stained paraffin sections revealed hall-marks of DAE with characteristic fine-granular aluminium-containing inclusions in the cytoplasm of plexus epithelia, cortical glia and neurons. Additionally, neurofibrillary tangles (NFT) and neuropil threads of the AD-type were demonstrated, consisting of paired helical filaments. No beta/A4 amyloid deposits were present. AD changes have been interpreted as age-related phenomena. Concerning the role of aluminium (Al) in AD, our morphological findings indicate that Al-induced DAE changes develop via different pathogenetic pathways compared to AD. Transferrin receptors stained positively in choroid plexus and neurons, in glial cells of the gray and white matter, in cerebellar (DAE-negative) Purkinje and granule cells as well as in AD-type NFT (and additionally in NFT of AD controls). This points to the ubiquitous distribution of transferrin receptors rather than to specific patterns in DAE and/or AD. Laser microprobe mass analysis indicated high Al-related signals at m/z 27, confirming the increase of Al in neurons with DAE. In contrast to the former clinically endemic and lethal dialysis encephalopathy, caused by massive Al-uptake by non-deionized dialysates, the term DAE comprises a morphological description in psychiatrically mostly unconspicious patients. It is characterized by the storage of argyrophilic degradation products of lysosomal-derived exclusively intracytoplasmic Al-containing inclusions, nowadays predominantly caused by long-term ingestion of Al-containing drugs in hemodialysis.