- The prominent death of central neurons in Alzheimer's and Parkinson's is reflected by changes in cell shape and by the formation of characteristic cytoskeletal inclusions (neurofibrillary tangles, Lewy bodies). This review focuses on the biology of neurofilaments and microtubule-associated proteins and identifies changes that can occur to these elements from basic and clinical research perspectives. Attention is directed at certain advances in neurobiology that have been especially integral to the identification of epitope domains, protein isoforms, and posttranslational (phosphorylation) events related to the composition, development, and structure of the common cytoskeletal modifications. Recently, a number of experimental strategies have emerged to simulate the aberrant changes in neurodegenerative disorders and gain insight into possible molecular events that contribute to alterations of the cytoskeleton. Descriptions of specific systems used to induce modifications are presented. In particular, unique neural transplantation methods in animals have been used to probe possible molecular and cellular conditions concerned with abnormal cytoskeletal changes in neurons.