Increased cystatin C in astrocytes of transgenic mice expressing the K670N-M671L mutation of the amyloid precursor protein and deposition in brain amyloid plaques.
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.
Steinhoff
T
T
Division of Psychiatry Research, University of Zurich, August-Forel Strasse 1, 8008 Zurich, Switzerland.
Moritz
E
E
Wollmer
M A
MA
Mohajeri
M H
MH
Kins
S
S
Nitsch
R M
RM
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
D016564:Amyloid beta-Protein Precursor; C525031:Cst3 protein, mouse; D055316:Cystatin C; D015891:Cystatins