Effects of apoE isoforms on beta-amyloid-induced matrix metalloproteinase-9 in rat astrocytes

Matrix metalloproteinase-9 (MMP-9) may play a role in the inflammatory glial response during Alzheimer's disease (AD). Astrocytes can degrade beta-amyloid (Aβ) and extracellular proteolysis via MMP-9 may be involved. Because Apolipoprotein E (APOE) genotype is an important factor for AD, we ask whether various apoE isoforms can influence Aβ-induced MMP-9 responses in primary rat astrocytes. Our data show that apoE4 significantly dampens Aβ-induced MMP-9 levels, possibly by downregulating the Rho–Rho kinase (ROCK) pathway. Reduction of astrocytic MMP-9 by apoE4 may affect Aβ clearance and promote Aβ deposition in AD.