ALTERATIONS IN GLIA AND AXONS IN THE BRAINS OF BINSWANGERS-DISEASE PATIENTS

Background and Purpose Although increasing attention is being paid to Binswanger's disease, a form of vascular dementia characterized by dif fuse white matter lesions? only limited information is available on th e pathological changes that occur in the glia and axons in the white m atter. We therefore investigated the brains of patients with Binswange r's disease to gain further insight into its pathophysiology. Methods Autopsied brains from patients with Binswanger's disease (group 3; n=1 7) were compared with those of non neurological controls (group 1; n=5 ) and controls with large cortical infarcts but without significant wh ite matter lesions (group 2; n=5). Glial fibrillary acidic protein (GF AP) was used as an immunohistochemical marker for astroglia, leukocyte common antigen (LCA) was used as a marker for microglia, and HLA-DR w as used as a marker for activated microglia. Axonal damage was assesse d by the accumulation of proteins, which are transported by fast axona l flow, amyloid protein precursor (APP), synaptophysin, and chromogran in A. Results Although there was no difference in numerical density of GFAP-immunoreactive astroglia in each group, regressive astroglia wer e observed in 7 of 17 patients with Binswanger's disease. LCA-immunore active microglia were 1.7 times more numerous in Binswanger's disease than in group 1 (P<.05). HLA-DR-immunoreactive-activated microglia wer e 3.4 times and 2.1 times more numerous in Binswanger's disease as com pared with group 1 (P<.01) and group 2 (P<.05), respectively. There wa s frequent perivascular lymphocyte cuffing, and clusters of macrophage s with a decreased number of oligodendroglia were observed in the rare fied white matter. The grading scores for the number of axons immunore active for either APP, synaptophysin, or chromogranin A were significa ntly higher in Binswanger's disease than in group 1 or 2. Conclusions The pathological alterations in Binswanger's diseased brains include r egressive changes in the astroglia and activation of the microglia wit h a decrease in the oligodendroglia, which were associated with the de gradation of both myelin and axonal components. These results indicate that an inflammatory reaction and compromised axonal transport, media ted by chronic ischemia, may play an important role in the pathophysio logy of Binswanger's disease.