Organization of the neurofilamentous network.

The neurofilamentous network of the normal rabbit brain (lateral vestibular nucleus) and of biopsies of human patients (cerebral cortex, sural nerve) was investigated electron microscopically. Thin sections of samples prepared by standard techniques and unfixed spreads of freshly isolated perikarya were utilized. The neurofilaments are assembled into a three-dimensional network associated with the axolemma, microtubules, mitochondria and polyribosomes. The elements of this network demonstrate helicity at several levels of organization. It is proposed that they are in a dynamic state of equilibrium between ordered lattice and open network paracrystalline states. Reversible phase transitions in the subunit proteins of the neurofilaments may lead to coiling and uncoiling of the filaments and induce alterations in the network structure of the neuroplasm. Giant axonal swellings in biopsies of the sural nerve are interpreted as accumulations of cytoskeletal elements in the absence of the orienting effect of microtubules. In cortical neurons of patients with Alzheimer's disease parts of the neurofilamentous network are in altered paracrystalline states; virus-like particles occur within this modified network. These concepts of cytoskeletal organization - network, helicity, phase transitions, and paracrystallinity - are useful for the interpretation of pathological alterations of the cytoskeleton and for an understanding of cytoskeletal organization in general.