The invention features a non-transgenic rat model for early AD, using a metal mixture of As, Cd and Pb, characterized by enhanced synergistic amyloidogenicity in rat cortex and hippocampus. This model can serve as a tool for (a) AD-directed drug screening, and (b) determining mechanism of AD pathogenicity. It features induction of the A?-mediated apoptosis and induction of inflammation in rodent brain. The invention features novel astrocyte and neuronal cellular models for AD, using a metal mixture of As, Cd and Pb, characterized by enhanced synergistic amyloidogenicity. This model can serve as a tool for (a) AD-directed drug screening in astrocytes and neurons, and (b) determining mechanism of AD pathogenicity in cells. It features induction of the A?-mediated apoptosis and induction of inflammation in astrocytes and neurons.