Increased Cystatin C in Astrocytes of Transgenic Mice Expressing the K670N-M671L Mutation of the Amyloid Precursor Protein and Deposition in Brain Amyloid Plaques

• Main Authors: Tiana Steinhoff, Eva Moritz, M.Axel Wollmer, M.Hasan Mohajeri, Stefan Kins, Roger M. Nitsch
• Format: Article
• Language: English
• Published: Elsevier 2001-08-01
• Series: Neurobiology of Disease
• Subjects: cystatin C; β-amyloid; Alzheimer disease; transgenic models
• Online Access: http://www.sciencedirect.com/science/article/pii/S0969996101904127

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 β-amyloid are colocalized in cortical blood vessels. To determine whether cystatin C and β-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 β-amyloid plaques, and discrete layers of cystatin C attached to amyloid plaque cores covered by a layer of β-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.