Astrocytic expression of the Alzheimer's disease beta-secretase (BACE1) is stimulus-dependent.
The beta-site APP-cleaving enzyme (BACE1) is a prerequisite for the generation of beta-amyloid peptides, which give rise to cerebrovascular and parenchymal beta-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 beta-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 beta-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 beta-amyloid plaques in the brains of aged Tg2576 mice and Alzheimer's disease patients.
Hartlage-Rübsamen
Maike
M
Department of Neurochemistry, Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany.
Zeitschel
Ulrike
U
Apelt
Jenny
J
Gärtner
Ulrich
U
Franke
Heike
H
Stahl
Tobias
T
Günther
Albrecht
A
Schliebs
Reinhard
R
Penkowa
Milena
M
Bigl
Volker
V
Rossner
Steffen
S
D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D001253:Astrocytes / Q000166:cytology / Q000201:enzymology*; D001921:Brain / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D010450:Endopeptidases; D005260:Female; D005911:Gliosis / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051381:Rats; D011917:Rats, Inbred Lew; D011918:Rats, Inbred SHR
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C509282:Bace1 protein, mouse; C509281:Bace1 protein, rat