One of the earliest neuropathological events in Alzheimer's disease is accumulation of astrocytes at sites of Aβ 1-42 depositions. Our results indicate that Aβ 1-42 toxic peptide increases lipid peroxidation, apoptosis and cell death in neurons but not in astrocytes in primary culture. Aβ 1-42-induced deleterious neuronal effects are not present when neurons and astrocytes are mixed cultured. Stimulation of astrocytes with toxic Aβ 1-42 peptide increased p-65 and decreased IκB resulting in inflammatory process. In astrocytes Aβ 1-42 decreases protein expressions of sirtuin 1 (SIRT-1) and peroxisome proliferator-activated receptor γ (PPAR-γ) and over-expresses peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1) and mitochondrial transcription factor A (TFAM), protecting mitochondria against Aβ 1-42-induced damage and promoting mitochondrial biogenesis.