Argentophilic neurofibrillary tangles were described in the cerebral cortex of Alzheimer's disease and later in the pigmented neurons in the brain stem of postencephalitic parkinsonism. In 1961, wide distribution of Alzheimer's neurofibrillary tangles in the central nervous system was observed in endemic fatal neurodegenerative diseases affecting the native Chamorro population on Guam: amyotrophic lateral sclerosis and parkinsonism-dementia complex on Guam. Abundant neurofibrillary tangles were found but no senile plaques. A topographic analysis of tangles in cases inGuam and at Montefiore were published in 1962 [23]. Thereafter, Alzheimer's neurofibrillary changes were documented in various areas of the nervous system of many other diseases. This communication is a brief review of the topographic investigation of Alzheimer's neurofibrillary changes. Occurrence of tangles in various conditions seems to indicate that various pathological agents can induce tangles. On the other hand, Alzheimer's neurofibrillary tangles, in general, show a rather striking predilection to affect particular neurons in the involved regions.