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(American Journal of Pathology. 1999;155:877-885.)
© 1999 American Society for Investigative Pathology

Regular Articles

Interaction of Aluminum with PHF in Alzheimer's Disease Neurofibrillary Degeneration Evidenced by Desferrioxamine-Assisted Chelating Autoclave Method

Harunobu Murayama^*, Ryong-Woon Shin^*, Jun Higuchi^*, Satoshi Shibuya^*, Tamaki Muramoto^* and Tetsuyuki Kitamoto^*

From the Department of Neurological Science,^*
Tohoku University School of Medicine; and the Department of Pathology,
Sendai City Hospital, Sendai, Japan

To demonstrate that aluminum III (Al) interacts with PHF in neurofibrillary degeneration (NFD) of Alzheimer's disease (AD) brain, we developed a "chelating autoclave method" that allows Al chelation by using trivalent-cationic chelator desferrioxamine. Its application to AD brain sections before Morin histochemistry for Al attenuated the positive fluorescence of neurofibrillary tangles, indicating Al removal from them. This method, applied for immunostaining with phosphorylation-dependent anti- antibodies, significantly enhanced the PHF immunoreactivity of the NFD. These results suggest that each of the phosphorylated epitopes in PHF are partially masked by Al binding. Incubation of AD sections with AlCl₃ before Morin staining revealed Al accumulation with association to neurofibrillary tangles. Such incubation before immunostaining with the phosphorylation-dependent anti- antibodies abolished the immunolabeling of the NFD and this abolition was reversed by the Al chelation. These findings indicate cumulative Al binding to and thereby antigenic masking of the phosphorylated epitopes of PHF. Al binding was further documented for electrophoretically-resolved PHF on immunoblots, indicating direct Al binding to PHF. In vitro aggregation by AlCl₃ was observed for PHF but was lost on dephosphorylation of PHF. Taken together, phosphorylation-dependent and direct PHF-Al interaction occurs in the NFD of the AD brain.

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