H. Tomimoto et al., REGRESSIVE CHANGES OF ASTROGLIA IN WHITE-MATTER LESIONS IN CEREBROVASCULAR-DISEASE AND ALZHEIMERS-DISEASE PATIENTS, Acta Neuropathologica, 94(2), 1997, pp. 146-152
The pathogenesis of white matter lesions, which are frequently found i
n ischemic cerebrovascular disease and Alzheimer's disease, remains un
clear. Using light and electron microscopic immunohistochemistry for g
lial fibrillary acidic protein (GFAP) as a marker, the present study f
ocused on the role of astroglia which show characteristic morphologica
l alterations. Of 29 brains of patients with cerebrovascular disease r
ind Alzheimer's disease, 4 brains showed extensive swelling and vacuol
ation of white matter astroglia with their processes disintegrated and
beaded (termed clasmatodendrosis). No such cells were observed in 6 c
ontrol patients. Clasmatodendritic astroglia were nor intensely eosino
philic using hematoxylin and eosin staining and included large lipophi
lic granules in their perikarya. These astroglia were immunoreactive f
or serum proteins such as immunoglobulins, fibrinogen and complement C
3, Clq and C3d, as well as or proteins which rue known to increase in
reactive astroglia, such as vimentin, alpha-B crystallin, apolipoprote
in-E and laminin. Double labeling for GFAP anti microglial cell marker
s indicated that these cells were of astroglial lineage. Immunoelectro
n microscopy for GFAP revealed that clasmatodendritic astroglia had co
ndensed chromatin, lysosomes and large membrane-bound osmiophilic cyto
plasmic inclusions, which corresponded to the lipophilic granules obse
rved with light microscopy. These cytochemical features collectively s
uggest that clasmatodendritic astroglia incorporate edema fluid and ph
agocytose cellular debris, and eventually degenerate as a result of ce
rebral edema.