Introduction The significance of Alzheimer's neurofibrillary changes has been actively discussed by neuropathologists over the past half a century, and numerous reports have been written concerning it. Their clinicoanatomical correlation with mental disease, their relation to senile plaques and other changes associated with aging, their cytological demonstration with silver impregnation techniques, as well as experimental attempts at their reproduction, have engaged many investigators. Topographic aspects of this neuronal alteration have been analyzed in certain parts of the central nervous system in a few conditions—the cerebral cortex in Alzheimer's disease and the senile psychoses, and the substantia nigra and brain stem in parkinsonism. Recent observations of neurofibrillary changes in 2 fatal neurologic diseases occurring on the island of Guam, the parkinsonism-dementia complex (Hirano, Kurland, Krooth, and Lessell1; Hirano, Malamud and Kurland2) and the amyotrophic lateral sclerosis syndrome (Malamud, Hirano and Kurland3), revealed their quite remarkable numbers and symmetric