Rosenthal fibers,eosinophilic inclusions,and anchorage densities with desmosome-like structures in astrocytes in Alzheimer's disease

Ultrastructural study of the cerebral cortex of nine brains of individuals with Alzheimer's disease (AD) revealed four types of pathological changes of astrocytes. Rosenthal fibers were found in three cases, eosinophilic inclusions in one, anchoraged densities with desmosome-like structures in two, and corpora amylacea in four. In two biopsies, Rosenthal fibers were seen in less than 5% of astrocytes, but in a third biopsy with numerous plaques, tangles, and severe neuronal loss, they were present in about 40% of astrocytes. In one case with severe AD pathology and numerous Rosenthal fibers, the cytoplasm of some astrocytes was occupied by inclusions composed of electron-dense granules 3–6 m in diameter or aggregates of inclusions greater than 12 m in diameter. Ultrastructurally, they were similar to eosinophilic inclusions observed in Aicardi syndrome and brain malformations. The presence of eosinophilic inclusions in the brain of elderly persons with Alzheimer's disease does not confirm the previous suggestion that this form of astrocyte pathology is typical for protoplasmic astrocytes and developmental brain malformations. Development anchorage densities associated with hemidesmosome-like structures, which reinforce astrocyte cell membranes facing the perivascular space, may reflect adaptation of astrocytes to the complex of changes that occurs in atrophic brain. Morphological changes in astrocytes in areas with numerous plaques and massive infiltration of intercellular space with -amyloid fibrils and remnants of neurons and ghost tangles suggest that astrocyte pathology is a late unspecific reaction to the cascade of changes induced by -amyloid deposition that causes neuronal degeneration and brain atrophy.Supported in part by funds from the New York State Office of Mental Retardation and Developmental Disabilities and a grant from the National Institutes of Health, National Institute of Aging No. P01-AGO-4220