Amyloid beta-protein (Abeta) is the major component of senile plaques that emerge in the cortex during aging and appear most abundantly in Alzheimer's disease. In the course of our immunocytochemical study on a large number of autopsy cases, we noticed, in many aged nondemented cases, the presence of unique diffuse plaques in the cortex distinct from ordinary diffuse plaques by immunocytochemistry. The former were amorphous, very faintly Abeta-immunoreactive plaques resembling diffuse plaques, but they stained for Abeta40 and were associated with small cells containing Abeta-positive granules. A panel of amino- and carboxyl-terminal-specific Abeta antibodies showed that such Abeta40-positive diffuse plaques and cell-associated granules were composed exclusively of amino-terminally deleted Abeta terminating at Abeta40, -42, and -43. Double immunostaining also showed that those Abeta-immunoreactive granules are located in astrocytes and not in microglia or neurons. Immunoelectron microscopy revealed that nonfibrillar Abeta immunoreactivity was located within lipofuscin-like granules in somewhat swollen astrocytes. These findings raise the possibility that astrocytes take up Abeta and attempt to degrade it in lysosomes in the aged brain.