ALTERATIONS OF THE BLOOD-BRAIN-BARRIER AND GLIAL-CELLS IN WHITE-MATTER LESIONS IN CEREBROVASCULAR AND ALZHEIMERS-DISEASE PATIENTS

Background and Purpose The underlying cause of white-matter lesions, w hich are frequent findings in cerebrovascular disease (CVD) and Alzhei mer's disease (AD), remains uncertain. We performed immunohistochemica l analysis of serum protein extravasation to investigate the function of the blood-brain barrier in white-matter lesions. Methods White-matt er lesions were estimated by use of Kluver-Barrera staining in patient s diagnosed clinicopathologically as having ischemic CVD (n=14) and AD (n=12) and from nonneurological control subjects (n=6). Axonal damage s were investigated by use of immunohistochemistry for amyloid protein precursor. Alteration of the blood-brain barrier was examined with fi brinogen and immunoglobulins used as markers. The numbers of HLA-DR-po sitive microglia and glial fibrillary acidic protein-positive astrogli a were examined comparatively. Results White-matter lesions were grade d as normal (grade 0) in 14 of the 32 cases (44%), slight (grade I) in 10 cases (31%), moderate (grade II) in 6 cases (19%), and severe (gra de III) in 2 cases (6%). Amyloid precursor protein was accumulated mos t frequently in grade II white-matter lesions. Immunohistochemistry fo r serum proteins labeled astroglial cell bodies and their processes, w hich seemed to have sequestered extravasated proteins. The groups with detectable white-matter lesions had significantly higher grading scor es for fibrinogen and immunoglobulins than the control group (P<.05). Although the higher scores for serum protein extravasation were statis tically significant in ischemic CVD cases (P<.05), there was no signif icant increase in AD cases. Activated microglia and astroglia were mor e numerous in the groups with white-matter lesions in both ischemic CV D and AD cases, although this increase in the number of astroglia was not evident in regions with clasmatodendrosis. Conclusions Dysfunction of the blood-brain barrier is more prominent in white-matter lesions seen in ischemic CVD than in AD and may have a role in the pathogenesi s of cerebrovascular white-matter lesions.