期刊
JOURNAL OF NEUROSCIENCE
卷 21, 期 5, 页码 1444-1451出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.21-05-01444.2001
关键词
alpha 1-antichymotrypsin; Alzheimer's disease; amyloid deposition; inflammation; transgenic mice; amyloid beta-peptide; Congo Red
资金
- NIA NIH HHS [R01 AG009665, AG09665] Funding Source: Medline
alpha (1)-Antichymotrypsin (ACT), an acute-phase inflammatory protein, is an integral component of the amyloid deposits in Alzheimer's disease (AD) and has been shown to catalyze amyloid beta -peptide polymerization in vitro. We have investigated the impact of ACT on amyloid deposition in vivo by generating transgenic GFAP-ACT-expressing mice and crossing them with the PDGF-hAPP/V717F mice, which deposit amyloid in an age-dependent manner. The number of amyloid deposits measured by Congo Red birefringence was increased in the double ACT/amyloid precursor protein (APP) transgenic mice compared with transgenic mice that only expressed APP, particularly in the hippocampus where ACT expression was highest, and the increase was preceded by elevated total amyloid beta -peptide levels at an early age. Our data demonstrate that ACT promotes amyloid deposition and provide a specific mechanism by which inflammation and the subsequent upregulation of astrocytic ACT expression in AD brain contributes to AD pathogenesis.
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