Male albino rats of Wistar strain (n=24) were assigned to three groups 2-month old (GRP I), 9-month old (GRP II) and 15-month old (GRP III) ,(n=8 in each ) in order to investigate age related changes in serum and brain samples. Malondialdehyde (MDA), reduced glutathione (GSH), acetylcholinesterase (AChE) and paraoxanase (PON) enzyme activites , soluble and aggregated amyloid β1-42 (Aβ1-42) levels were analyzed in brain tissues. Tissues were also stained with Congo-red dye in order to observe fibrillation. Serum total cholesterol, uric acid and triglyceride levels and PON activites were investigated. Serum uric acid levels were significantly decreased (p<0.05) whereas total cholesterol and triglyceride levels were increased (p<0.01) in GRP III rats. Tissue MDA and GSH concentrations did not change significantly among groups. Free Aβ1-42 concentrations and fibrillation were both significantly increased in brain tissues in GRP III (p<0.05). Tissue AChE activities were significantly reduced (p<0.05) and PON activities did not change among goups. Our serum results indicated an age related systemic oxidative stress. Brain results did not show an oxidative stress in terms of lipid peroxidation but the decreased AChE activites, unaltered PON activities accompanied with increased amyloidogenesis is accepted as an early response of neurodegeneration in older rats.