References
Query Results -- Details
MGI Accession ID: MGI:3722924
J Number: J:124911
Other Accession IDs:
Title: Induction of complement proteins in a mouse model of cerebral microvascular Abeta deposition.
Authors: Fan R; Defilippis K; Van Nostrand WE
Journal: J Neuroinflammation
Volume: 4
Issue: 1
Date: 2007 Sep 18
Year: 2007
Pages: 22
Review Status: Peer Reviewed
Abstract:
ABSTRACT: The deposition of amyloid beta-protein (Abeta) in cerebral vasculature, known as cerebral amyloid angiopathy (CAA), is a common pathological feature of Alzheimer's disease and related disorders. In familial forms of CAA single mutations in the Abeta peptide have been linked to the increase of vascular Abeta deposits accompanied by a strong localized activation of glial cells and elevated expression of neuroinflammatory mediators including complement proteins. We have developed human amyloid-beta precursor protein transgenic mice harboring two CAA Abeta mutations (Dutch E693Q and Iowa D694N) that mimic the prevalent cerebral microvascular Abeta deposition observed in those patients, and the Swedish mutations (K670N/M671L) to increase Abeta production. In these Tg-SwDI mice, we have reported predominant fibrillar Abeta along microvessels in the thalamic region and diffuse plaques in cortical region. Concurrently, activated microglia and reactive astrocytes have been detected primarily in association with fibrillar cerebral microvascular Abeta in this model. Here we show that three native complement components in classical and alternative complement pathways, C1q, C3, and C4, are elevated in Tg-SwDI mice in regions rich in fibrillar microvascular Abeta. Immunohistochemical staining of all three proteins was increased in thalamus, hippocampus, and subiculum, but not frontal cortex. Western blot analysis showed significant increases of all three proteins in the thalamic region (with hippocampus) as well as the cortical region, except C3 that was below detection level in cortex. Also, in the thalamic region (with hippocampus), C1q and C3 mRNAs were significantly up-regulated. These complement proteins appeared to be expressed largely by activated microglial cells associated with the fibrillar microvascular Abeta deposits. Our findings demonstrate that Tg-SwDI mice exhibit elevated complement protein expression in response to fibrillar vascular Abeta deposition that is observed in patients with familial CAA.
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