A Morphometric study of subcortical neurofibrillary tangles in Alzheimer's disease


Department of Neuropsychiatry, Hyogo college of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663, Japan


The numbers of neurofibrillary tangles(NFT) in the subcortical nuclei detected in Gallyas-Nissl double stained sections was evaluated with computer-based image analysis techniques. This was undertaken to examine the susceptibility to NFT formation and to identify mutual correlations in NFT formation among the basal ganglia in Alzheimer's disease (AD). The numbers of NFT are insufficient to compare the regional differences of NFT in each nucleus of the AD brains because large subcortical gray nuclei tend to have more NFT, Incidences of NFT were given definitions in order to find the NFT incidences for the expected neuronal populations, The definitions used were: the ratio of total numbers of NFT observed in a given subcortical gray nucleus of AD brains to the total numbers of medium- to large-sized neurons(≥ 150μm2) in which the nucleoli were confirmed in the corresponding structure of control brains. A common order of susceptibility to NFT changes was found among the subcortical nuclei in advanced stages of AD cases, According to NFT incidences, subcortical nuclei were classified into four groups. The highest incidence of NFT (88%) was found in the nucleus basalis of Meynert. The severely affected group (NFT Incidences; 28–44%) included the raphe nucleus (superior central nucleus), anterior thalamic nucleus (anterior ventral thalamic nucleus), locus ceruleus and claustrum, The putamen, substantia nigra (zona compacta), medial thalamic nucleus (medio-dorsal thalamic nucleus) and lateral thalamic nucleus (ventro-lateral and ventro-anterior thalamic nuclei) comprised the moderately affected group (NFT incidences; 9–15%). The substantia nigra (zona reticulata), globus pallidus, subthalamic nucleus and red nucleus constituted the slightly affected group (NFT incidences;<5%). In spite of the group classifications, no significant mutual correlations in NFT incidences between any pair of subcortical nuclei were indicated. The present study suggests that the NFT formations in AD take place in the subcortical nuclei according to individual susceptibility, irrespective of the connections between the nuclei.