HEPATOCYTE GROWTH-FACTOR (HGF SF) IN ALZHEIMERS-DISEASE/

Hepatocyte growth factor (HGF/SF), is a heparin-binding polypeptide wh ich stimulates DNA synthesis in a variety of cell types and also promo tes cell migration and morphogenesis. HGF/SF mRNA has been found in a variety of tissues, including brain. In a previous study, we showed th at basic fibroblast growth factor (bFGF), another heparin-binding prot ein is increased in Alzheimer's disease (AD), and appears to be associ ated with the heparan-sulfate proteoglycans bound to B/A(4) amyloid (B iochem. Biophys. Res. Commun. 171 (1990) 690-696). In the present stud y, we examined the distribution of HGF/SF in 4% paraformaldehyde fixed samples of prefrontal cortex from control and Alzheimer patients, in order to assess the possibility that HGF/SF may be found in associatio n with the pathologic changes which occur in Alzheimer's disease. A sp ecific polyclonal antibody directed against HGF/SF revealed widespread HGF/SF-like immunoreactivity in both the cerebral cortex and white ma tter. Confocal microscopy confirmed that HGF/SF could be found in both GFAP positive astrocytes and LN3 positive microglia cells, as well as rare scattered cortical neurons. In the AD cases studied, the immunor eactivity was increased within both the astrocytes and microglial cell s surrounding individual senile plaques. No staining was seen within t he neurofibrillary tangles. Western blot analysis confirmed the normal molecular form of HGF/SF in Alzheimer's disease. Quantitative ELISA a ssay demonstrated a significant increase in HGF/SF in AD relative to a ge matched controls. These studies confirm the presence of HGF/SF immu noreactivity within neurons, astrocytes and microglial cells. They als o indicate that HGF/SF may be increased within senile plaques as a fun ction of the gliosis and microglial proliferation which occurs in asso ciation with these structures in Alzheimer's disease. (C) 1998 Elsevie r Science B.V.