Neurofibrillary pathology: current status and research perspectives

The neurofibrils seen in the light microscope are shown, by electron microscopy, to be heterogeneous structures, formed of neurotubules and neurofilaments. A variety of pathological conditions (especially, presenile and senile dementia (are characterized by the presence of neurofibrillary tangles, formed either of paired helical filaments or of single filaments. The morphology, distribution and biochemistry of these various fibrillary structures is reviewed. Particular attention is devoted to the assembly of neurotubules, to the mechanism of action of drugs which prevent assembly, and to possible implications for the experimental induction of neurofibrillary pathology. Of central importance in the arguments is the emphasis on the normal neurofibrillary structures being single forms of pleomorphic proteins. The healthy neuron assembles these proteins into the required form as is necessary for the needs of that neuron. Interference with this process in neuronal cell biology may lead to the deposition of neurofibrillary tangles. On the basis of the morphological and biochemical evidence, several approaches to the experimental study of neurofibrillary pathology are proposed.