Neurofibrillary tangles, aluminum

Neurofibrillary tangles, aluminum associate with, 36 416-417 Neuromodulin, 46 449 Neuromuscular blocking agents, 36 7 Neuron-specific calcium sensor (NCS) proteins, 46 457... 

A sufficient animal model for human Alzheimer s disease has not been developed. Although animals, particularly rabbits, exposed to aluminum develop neurofibrillary tangles (Crapper-McLachlan and... 

Candy JM, McArthur FK, Oakley AE, et al. 1992. Aluminum accumulation in relation to senile plaque and neurofibrillary tangle formation in the brains of patients with renal failure. J Neurol Sci 107 210-218. 

Good PF, Perl DP, Bierer LM, et al. 1992b. Selective accumulation of aluminum and iron in the neurofibrillary tangles of Alzheimer s disease A laser microprobe (LAMMA) study. Ann Neurol 31 286-292. 

Makjanic J, McDonald B, Chen CPLH, et al. 1998. Absence of aluminum in neurofibrillary tangles in Alzheimer s disease. Neurosci Lett 240 123-125. 

Perl DP, Brody AR. 1980. Alzheimer s disease X-ray spectrometric evidence of aluminum accumulation in neurofibrillary tangle-bearing neurons. Science 208 297-299. 

Singer SM, Chambers CB, Newby GA, et al. 1997. Tau in aluminum-induced neurofibrillary tangles. Neurotoxicology 18 63-76. 

Abreo K, Abreo F, Sella ML, Jain S (1999) Aluminum enhances iron uptake and expression of neurofibrillary tangle protein in neuroblastoma cells. J Neurochem 72 2059-2064... 

In 1937, a study found that aluminum salts caused uniformly fatal, neurotoxic symptoms when injected intracerebrally in animals (Scherp and Church 1937). Experimental work in the 1960s later showed that intracerebral or intrathecal injections of aluminum in rabbits caused neurotoxic reactions and neurofibrillary tangles (NFTs) similar to those observed in Alzheimer s disease (AD) (Klatzo et al. 1965 Terry and Pena 1965). Between 1973 and 1976, three landmark articles reported aluminum in the NFTs of AD patients (Crapper 1974 Crapper et al. 1973, 1976). 

Perl DP, Munoz-Garcia D, Good PF, et al Intracytoplasmic aluminum accumulation in neurofibrillary tangle-bearing neurons detection by laser microprobe mass analyzer (abstract). Ann Neurol 18 143, 1985... 

Environmental and nutritional factors may also affect the development of Alzheimer disease and other mental illness. Aluminum frequently accumulates in the neurons containing neurofibrillary tangles. Copper and zinc ions can cause the amyloid Ap to aggregate. However, Zn + may actually protect against neurotoxicity. The amino acid P-N-methylamino-L-alanine, a constituent of the toxic seeds of a type of palm Cycas circimlis L.), may have induced both AES and Guam disease, a condition resembling Parkinson disease, in a population in Guam that traditionally used these seeds as food. ... 

Garruto RM, Fukatsu R, Yanagihara R, Gajdusek DC, Hook G Fiori CE. (1983). Imaging of calcium and aluminum in neurofibrillary tangle-bearing neurons in parkinsonism-dementia of Guam. Proc Natl Acad Sci USA 81, 1875-1879. 

Guy SP, Jones D, Mann DMA, Itzhaki RF (1991) Human neuroblastoma cells treated with aluminium express, an epitope associated with Alzheimer s disease neurofibrillary tangles. Neurosci Lett 121 166-168 Hollosi M, Urge L, Perczel A, Kajtar J, Teplan I, Otvos L Jr, Fasman GD (1992) Metal ion-induced conformational changes of phosphorylated fragments of human neurofilament (NF-M) protein. J Mol Biol 223 673-682 Huang Y-P, Bittar EE (1991) Protection by GTP from the effects of aluminum on the sodium efflux in barnacle muscle fibers. Biochim Biophys Acta 1062 255-263 Huber CT, Frieden E (1970) The inhibition of ferroxidase by trivalent and other metal ions. J Biol Chem 245 3979-3984... 

Terry and Pena " reported that aluminum was concentrated in the region of the neurofibrillary tangles in aluminum exposed rabbits. Similarly, Klatzo et al." used the solochrome Azurine method to stain for aluminum in aluminum phosphate-injected rabbits. The observed faint, but unmistakably positive blue staining for aluminum in the aroa corresponding to the presence of the birofiingent neurofibrillary tangles in the affected neurons. 

In contrast to the nuclear binding of aluminum in senile dementia, the aluminum in dialysis dementia patients has been reported to be primarily cytoplasmic. This is of particular interest, for in dialysis dementia patients, neurofibrillary tangles have not been observed to accompany increased aluminum concentrations. It is tempting to speculate that the differential cellular responses to aluminum might be caused by different binding sites for aluminum within the ceU. 

Increased brain aluminum accumulation is known to be associated with neurofibrillary tangles in some species. The terms neurofibrillary tangle or "neurofibrillary degeneration refer to an accumulation of tangles of neurofibers within the neuron. Electron microscopic examination of aluminum-induced neurofibrillary tangles indicates that they consist of areas of cytoplasmic clearings, filled with either compact orderly bundles or accumu-... 

The results of controlled exposure of human neurons to eilu-minum in vitro have been reported by DeBoni et al. The dorsal root ganglion neurons remained uneffected by aluminum exposure, while neocortical cells showed an accumulation of neurofibrillary tangles with aluminum exposure in the concentration range found in Alzheimer s disease. However, the observed tangles were an accumulation of 10 nm neurofilaments identical to those seen with aluminum exposure in animeds and not like the paired helical filaments seen in Alzheimer s disease. Paired helical filaments have been induced (in vitro) in human neurons by the same researchers, but as a result of exposure to Alzheimer brain extract, and in the absence of aluminum. ... 

Therefore, there appears to be considerable evidence to suggest that elevated aluminum may be the precipitating neuropathological event in dialysis dementia, while aluminum may be a secondary event in Alzheimer s disease. That neurofibrillary tangles are not found with the extremely elevated aluminum levels seen in dialysis dementia would appear to be inconsistent with the reported production of such tangles with elevated aluminum in human neurons in vitro. Unfortunately, it is not possible to reconcile these two findings at this time. Clearly, much more work needs to be done to clarify further the possible role of aluminum in human disease. 

The most frequently used method to assay for the neuropathological effects of aluminum is the neuroanatomical verification of neurofibrillary tangles. This can be done either at the light or electron microscopic level. 

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