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.