Glial involvement in the degeneration process of Lewy body-bearing neurons and the degradation process of Lewy bodies in brains of dementia with Lewy bodies.

Glial involvement in the degeneration process of Lewy body (LB)-bearing neurons and the degradation process of LBs in the cerebral cortex and amygdala in brains of dementia with Lewy bodies was investigated immunohistochemically. HLA-DR-positive microglia frequently extended their processes to degenerated neurons with alpha-synuclein-positive LBs, while some GFAP-positive astroglial processes attached to weakly alpha-synuclein-positive extracellular LBs. Some intracellular LBs were immunoreactive to anti-C4d antibody, and these LB-bearing neurons were involved by activated microglia. About half of the intracellular LBs were immunoreactive to anti-chromogranin-A (CGA) 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 stimulation, in the degeneration process of LB-bearing neurons, some intracellular LBs were immunoreactive to the antibody to NF-kappaB, a transcriptional factor activated by cytokines. These findings suggest that microglia participate in the degeneration process of LB-bearing neurons via varying immunogenic elements including complement proteins, CGA and probably some cytokines, and that astroglia participate in the degradation process of LBs.