Do aluminium and/or glutamate induce Alzheimer PHF-like formation? An electron microscopic study.

Paired helical filaments (PHFs) constitute the majority of filaments in neurofibrillary tangles (NFTs), an Alzheimer's disease (AD) characteristic. PHFs consists of two filaments helically twisted around one another in a regular pattern. The effects of possible PHF-inducing candidates, namely aluminium and glutamate, were observed at the ultrastructural level in this investigation. Rat cerebral explants were exposed to aluminium, citric acid and glutamate singly or combined from 7-12 days in vitro (DIV), while control explants remained in basal medium. On 12 DIV, explants were processed for EM. Three-four EM explants were serially sectioned per condition. Ten 60 nm sections from five systematically sampled areas per explant were collected. One section was randomly chosen per sampled area and all neurons within it observed at 81,200x to record the presence of accumulations of curved filaments (CFs), straight filaments (SFs) or PHFs. Using stereological methods, absolute numbers and the percentage incidence of CFs and SFs were calculated. A significant increase in the frequency of neurons containing CF aggregations in aluminium explants compared to glutamate explants was found. There were no significant differences between conditions for neurons containing SF accumulations. Possible PHFs were observed in one aluminium/glutamate-treated explant. These results suggest that aluminium alone can cause significant formation of accumulations of C- or S-shaped CFs, some of which are double-stranded and twisted around one another regularly. However, structures that were possibly PHF-like were only observed in one aluminium-treated explant, thus making it premature to draw an association between aluminium and the induction of AD-like pathology.