Glial involvement in the degeneration process of Lewy body-bearing neuronsand the degradation process of Lewy bodies in brains of dementia with Lewybodies

Glial involvement in the degeneration process of Lewy body (LB)-bearing neu rons and the degradation process of LBs in the cerebral cortex and amygdala in brains of dementia with Lewy bodies was investigated immunohistochemica lly. HLA-DR-positive microglia frequently extended their processes to degen erated neurons with alpha -synuclein-positive LBs, while some GFAP-positive astroglial processes attached to weakly alpha -synuclein-positive extracel lular LBs. Some intracellular LBs were immunoreactive to anti-C4d antibody, and these LB-bearing neurons were involved by activated microglia. About h alf of the intracellular LBs were immunoreactive to anti-chromogranin-A (CG A) antibody, and most of CGA-positive LB-bearing neurons were surrounded by microglia. Although we could find no evident participation of TNF-alpha, a candidate cytokine that is up-regulated by microglia following CGA stimula tion, in the degeneration process of LB-bearing neurons, some intracellular LBs were immunoreactive to the antibody to NF-kappaB, a transcriptional fa ctor activated by cytokines. These findings suggest that microglia particip ate in the degeneration process of LB-bearing neurons via varying immunogen ic elements including complement proteins, CGA and probably some cytokines, and that astroglia participate in the degradation process of LBs. (C) 2001 Elsevier Science B.V. All rights reserved.