. Experimental production of neurofibrillary degeneration. 2. Electron microscopy, phosphatase histochemistry and electron probe analysis. J Neuropathol Exp Neurol. 1965 Apr;24:200-10.



During a search for an experimental counterpart of the spongy change (1) of Creutzfeld-Jakob syndrome, Klatzo's alum~phosphate technic (2) was called to our attention. At that time it was thought to produce an unusual cytoplasmic vacuolation. The first electron micrographs revealed remarkable neurofibrillary aggregates instead of vacuoles, and silver impregnations for light microscopy followed, confirming this observation. Serendipity appears to be moderately common in the history of science, but is rarely experienced by individual investigators. We can only be grateful for it.

The neurofibrillary degeneration found in alum-treated rabbits bears considerable resemblance to the Alzheimer's tangles of human dementia (3, 4). There are differences as to structure as well as genesis, but it is hoped that further analysis of these differences will shed light on the nature and origin of the human lesion.


1. Electron microscopy has demonstrated the fibrillar content of the neuronal lesions in rabbits treated with alum phosphate.
2. The filaments involved in these Alzheimer-like tangles are less than 150 A wide, have side branches, and are perhaps tubular. They are similar to the filaments found in the human disease.
3. Traces of aluminum were found in the affected rabbit neurons by the Philips Electron Probe Analyzer. Neither aluminum nor other elements were found by similar analysis of human neurofibrillary tangles.
4. The alum-induced tangles are contrasted with the lesions in distended axons of rats treated with imidodiproprionitrile.


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