Role of hepatocyte growth factor in the pathoetiology of Alzheimer's disease

点击翻译按钮获取中文摘要

Hepatocyte growth factor (HGF) activator (HGFA) has been identified as a key enzyme that regulates the activity of HGF in vivo. Two types of HGFA inhibitor, type 1 (HAI-1) and type 2 (HAI-2), have been purified as potent inhibitors of HGFA.Our previous studies have shown that white matter astrocytes produce HGF, HGFA and HAI-1. We examined HAI-2 immunolabelling in the brains of neurologically normal persons and patients with Alzheimer's disease (AD). Furthermore, we identified the expression of the mRNA for HAI-2 by in situ hybridization histochemistry. The HAI-2 antibody stained astrocytes in all brain tissues. Expression of the mRNA for HAI-2 was also seen in astocytes. The intensities of the HAI-2 immunoreactivity and the signal for HAI-2 mRNA were similar in AD and normal control brains. These results suggest that almost all the astrocytes produce HAI-2. This is different from HAI-1 which appears to be produced only by white matter astrocytes.We also examined the level of HGF in cerebrospinal fluid (CSF) from AD and age matched disease control patients by a newly developed enzyme-linked immunoabsorbent assay system. Consistent with the immunohistochemical data, a significantly higher concentration of HGF in AD CSF was found as compared with controls. In both groups, a significant correlation was seen between CSF HGF levels and white matter high-signal foci detemined on brain MRI.These results suggest that CSF HGF levels could reflect the white matter damage.