title: Astrocytes containing amyloid beta-protein (Abeta)-positive granules are associated with Abeta40-positive diffuse plaques in the aged human brain.
abstract: 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.
authors.affiliation: Department of Neuropathology, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Funato
authors.forename: M
authors.initials: M
authors.lastname: Yoshimura
authors.forename: T
authors.initials: T
authors.lastname: Yamazaki
authors.forename: T C
authors.initials: TC
authors.lastname: Saido
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.forename: J
authors.initials: J
authors.lastname: Yokofujita
authors.forename: R
authors.initials: R
authors.lastname: Okeda
authors.forename: Y
authors.initials: Y
authors.lastname: Ihara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism* / Q000648:ultrastructure; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006131:Growth Inhibitors / Q000378:metabolism; D006801:Humans; D008062:Lipofuscin / Q000378:metabolism; D000090023:Metallothionein 3; D008854:Microscopy, Electron; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000648:ultrastructure; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D005904:Glial Fibrillary Acidic Protein; D006131:Growth Inhibitors; D008062:Lipofuscin; D000090023:Metallothionein 3; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)