title: Increased cystatin C in astrocytes of transgenic mice expressing the K670N-M671L mutation of the amyloid precursor protein and deposition in brain amyloid plaques.
abstract: Cystatin C is an essential secretory cofactor for neurogenesis with potent protease inhibitor activities. Polymorphisms of cystatin C are genetically associated with Alzheimer's disease (AD), and the L68Q mutation causes hereditary cerebral hemorrhage with amyloidosis of the Icelandic type, in which cystatin C and beta-amyloid are colocalized in cortical blood vessels. To determine whether cystatin C and beta-amyloid also colocalize in brain amyloid plaques, we analyzed transgenic mice expressing the Swedish APP (SweAPP) mutation. We found high levels of cystatin C in astrocytes surrounding beta-amyloid plaques, and discrete layers of cystatin C attached to amyloid plaque cores covered by a layer of beta-amyloid. In addition, cystatin C accumulated in reactive astrocytes throughout the brain, independently of, and before the onset of, amyloid plaque formation. These results show that expression of SweAPP is associated with increased cystatin C in reactive astrocytes, and they suggest an early role of cystatin C in appositional amyloid plaque growth.
authors.affiliation: Division of Psychiatry Research, University of Zurich, August-Forel Strasse 1, 8008 Zurich, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Steinhoff
authors.forename: E
authors.initials: E
authors.lastname: Moritz
authors.forename: M A
authors.initials: MA
authors.lastname: Wollmer
authors.forename: M H
authors.initials: MH
authors.lastname: Mohajeri
authors.forename: S
authors.initials: S
authors.lastname: Kins
authors.forename: R M
authors.initials: RM
authors.lastname: Nitsch
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000235:genetics*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D055316:Cystatin C; D015891:Cystatins / Q000032:analysis / Q000378:metabolism*; D015870:Gene Expression; D051379:Mice; D008822:Mice, Transgenic; D016296:Mutagenesis; D058225:Plaque, Amyloid / Q000737:chemistry / Q000378:metabolism / Q000473:pathology
chemical_list: D016564:Amyloid beta-Protein Precursor; C525031:Cst3 protein, mouse; D055316:Cystatin C; D015891:Cystatins