Alexander's disease: further light-, and electron-microscopic observations

Abstract

The neuropathologic and ophthalmopathologic findings in a 5 3/4-year-old boy with Alexander's disease are reported. Light- and electron-microscopic and immunohistochemical studies revealed that (1) the granular osmiophilic deposits (GOD) in Alexander's disease accumulate mainly in astrocytic processes to form Rosenthal fibers, (2) the Bergmann glia are different in this regard and accumulate the deposits primarily in their perikarya, (3) the Müller cells of retina (which closely resemble astrocytes) do not accumulate GOD, (4) the deposits are also not present in other glial cells and glial-like cells such as pituicytes and pineocytes, (5) the deposits are sparse in the retrobulbar optic nerves, and (6) the peroxidase-antiperoxidase and immunofluorescence studies do not demonstrate glial fibrillary acidic protein (GFAP), albumin, immunoglobulins, or fibrinogen in the astrocytic deposits. The different deposition of GOD in various cytoplasmic regions of astrocytes in different areas of central nervous system (CNS) suggests that astrocyte metabolism may not be uniform throughout the brain. Attention to this point may prove helpful in understanding the pathogenesis of the deposits in Alexander's disease. The absence of immunohistochemically demonstrable plasma proteins and GFAP in the astrocytic GOD indicates that the latter have an origin different from plasma proteins and glial filaments. Alternatively, the deposits may be derived from these proteins, but their antigenicity has since been altered.