Astrocytic expression of the Alzheimer's disease β-secretase (BACE1) is stimulus-dependent

• Published in: Glia Vol. 41; no. 2; pp. 169 - 179
• Main Authors: Hartlage-Rübsamen, Maike, Zeitschel, Ulrike, Apelt, Jenny, Gärtner, Ulrich, Franke, Heike, Stahl, Tobias, Günther, Albrecht, Schliebs, Reinhard, Penkowa, Milena, Bigl, Volker, Roßner, Steffen
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 15-01-2003; Wiley-Liss
• Subjects: aging; Aging - metabolism; Alzheimer Disease - enzymology; Alzheimer Disease - pathology; Alzheimer Disease - physiopathology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; amyloid plaques; Amyloid Precursor Protein Secretases; Animals; Animals, Newborn; Aspartic Acid Endopeptidases - metabolism; astrocytes; Astrocytes - cytology; Astrocytes - enzymology; Biological and medical sciences; Brain - enzymology; Brain - pathology; Brain - physiopathology; Brain Ischemia - enzymology; Brain Ischemia - pathology; Brain Ischemia - physiopathology; Cells, Cultured; cholinergic immunolesion; confocal laser scanning microscopy; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental - enzymology; Encephalomyelitis, Autoimmune, Experimental - pathology; Encephalomyelitis, Autoimmune, Experimental - physiopathology; Endopeptidases; experimental autoimmune encephalomyelitis; Female; gliosis; Gliosis - enzymology; Gliosis - pathology; Gliosis - physiopathology; Humans; immunocytochemistry; lesion paradigms; LPS injection; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurology; Rats; Rats, Inbred Lew; Rats, Inbred SHR; viral infection; β-secretase; Senescence; viral infection; Alzheimer disease; Neuroglia; Central nervous system; experimental autoimmune encephalomyelitis; confocal laser scanning microscopy; β-secretase; Degenerative disease; gliosis; Alzheimer's disease; cholinergic immunolesion; Human; LPS injection; Nervous system diseases; lesion paradigms; Enzyme; Rodentia; immunocytochemistry; Astrocyte; Gene expression; In vitro; Cerebral disorder; amyloid plaques; Vertebrata; Mammalia; Mouse; Animal; Central nervous system disease; aging; astrocytes; Brain (vertebrata)
• ISSN: 0894-1491; 1098-1136
• DOI: 10.1002/glia.10178

The beta‐site APP‐cleaving enzyme (BACE1) is a prerequisite for the generation of β‐amyloid peptides, which give rise to cerebrovascular and parenchymal β‐amyloid deposits in the brain of Alzheimer's disease patients. BACE1 is neuronally expressed in the brains of humans and experimental animals such as mice and rats. In addition, we have recently shown that BACE1 protein is expressed by reactive astrocytes in close proximity to β‐amyloid plaques in the brains of aged transgenic Tg2576 mice that overexpress human amyloid precursor protein carrying the double mutation K670N‐M671L. To address the question whether astrocytic BACE1 expression is an event specifically triggered by β‐amyloid plaques or whether glial cell activation by other mechanisms also induces BACE1 expression, we used six different experimental strategies to activate brain glial cells acutely or chronically. Brain sections were processed for the expression of BACE1 and glial markers by double immunofluorescence labeling and evaluated by confocal laser scanning microscopy. There was no detectable expression of BACE1 protein by activated microglial cells of the ameboid or ramified phenotype in any of the lesion paradigms studied. In contrast, BACE1 expression by reactive astrocytes was evident in chronic but not in acute models of gliosis. Additionally, we observed BACE1‐immunoreactive astrocytes in proximity to β‐amyloid plaques in the brains of aged Tg2576 mice and Alzheimer's disease patients. GLIA 41:169–179, 2003. © 2003 Wiley‐Liss, Inc.