Association of Ubiquitin-Positive Neuritic Threads in the CA 2-3 Region of the Hippocampus with Cortical Lewy Bodies

Yang, Ki Hwa; Yang, Ki Seung; Kang, Choong Gu; Sung, Joo Ho

Abstract

Ubiquitin-positive neuritic threads (UNTS) in the hippocampal CA 2-3 region are reported to occur exclusively in association with so-called diffuse Lewy body disease (DLBD). hi order to assess the association between the occurrence of Lewy bodies (LBs) and that of the UNTs, an immunohistochemical study on the hippocampus including the parahippocampal gyrus with antiubiquitin antibody (Chemicon Co., California, U.S.A.) was perfon-ned in four groups of patient's brains. All brains were selected from the large pool of brains referred to the Neuropadiology Laboratory of the University of Minnesota for studies of Alzheimer's disease. Group 1 consisted of 34 cases (20 male and 14 female) with LBs widespread in the frontal and temporal cortex and the brain stem nuclei (basal nucleus, substantia nigra, locus ceruleus and dorsal vagal nucleus) associated with varying degrees of degeneration of the substantia nigra; 21 (11 male and 10 female) combined with and 13 (9 male and 4 female) without Alzheimer's disease (AD) pathology. Group 2 included 12 cases (9 male and 3 female) in which LBs were observed only in the brain stem nuclei; 7 with and 4 without AD pathology. Group 3 consisted of 30 cases (9 male and 21 female) without LBs but with AD pathology and degeneration of the substantia nigra. Group 4 included 23 cases (11 male and 12 female) with neither LBs nor AD pathology but with degeneration of the substantia nigra. Ages of the patients varied among the groups. In the 46 cases in the first two groups with LBs. The mean age in the 28 cases with AD pathology was 77.3+/-8.9 and in the 18 cases without AD pathology it was 71.6+/-8.8 (P<0.05). In the 53 cases in groups 3 and 4 without LBs, which served as the controls, the mean ages were 80.8+/-7.7 and 74.0+/-9.7 respectively. UNTs were encountered in all (100%) of 34 cases of group I with widespread LBs which met the histological criteria of DLBD regardless of combined AD pathology. In 12 cases of group 2 with LBs confined to the brain stem, UNTs occurred in 3 (25%), 1 with and 2 without AD pathology. hi the group 3 cases with only AD pathology, UNTs occurred in 4 (13%) of 30 cases, while no UNTs were encountered in the 23 cases of group 4 without AD pathology or LBs. In conclusion, UNTs in the hippocampal CA 2-3 region occur invariably but not exclusively in association with widespread LBs, frequently when LBs are confined to the brain stem, and infrequently with AD pathology. It seems, therefore, that the UNTs are closely related to LBs and increase in ftequency as LBs spread beyond the brain stem with time, but the pathogenesis of the UNTs is little understood.