Some recent investigations have suggested that a breakdown in the structure of semantic knowledge is an attribute that characterizes the cognitive deficits of Alzheimer's disease (AD). Two studies were conducted to examine the organization of the semantic knowledge by multidimensional scaling, clustering and Pathfinder analyses. The results suggested that AD patients exhibited a significant deterioration in the structure of their semantic knowledge. The organization of their semantic knowledge is characterized by abnormal clusterings of concepts and atypical strength of associations. In addition, while AD patients focus primarily on concrete conceptual information, NC subjects stress abstract conceptual knowledge in organizing concepts. Given that semantic knowledge is presumably stored and distributed in the neocortex, I and my colleagues hypothesized that the observed structural alteration is most likely a reflection of the degeneration in the patients' neocortical systems. To test this hypothesis, I extended the previous experiment to include Huntington's disease (HD) and Amnesic (AM) patients. These two groups of patients were chosen because they share some common neurological symptoms with AD patients and yet their neocortical systems are relatively intact. HD, like AD, is a dementing illness, but the pathological change of HD involves primarily the subcortical region. AM, like AD, is characterized by impairment in learning new information, but the pathological change in AM is focused in the mesial temporal region. If the structural alteration in semantic knowledge is a unique characteristic of AD but is not an attribute of all forms of dementing illness or all kinds of memory disorder, then the organization of semantic knowledge of HD and AM patients will be essentially normal. The results of this experiment suggested that the semantic networks in AD patients, but not those in HD and AM patients, are characterized by abnormal clustering of concepts and atypical strength of associations. In addition, while HD and AM subjects, like control subjects, categorize concepts primarily along an abstract conceptual dimension, AD patients focus on a concrete perceptual dimension in categorizing concepts. These results support the notion that the integrity of the neocortex is necessary for organizing semantic knowledge.