Four microtubule associated proteins (MAP2, MAP1B, MAP1A, tau) from rat brain cortex were analyzed at 6, 12 and 24 months for age-related changes in total expression, microtubule (MT) binding ability, sensitivity to endogenous calpain-like degradation and heat stability (MAP2, tau). No significant change in cortical MAPs levels were found between 12 and 24 months of age. However, small increases in MAP2, MAP1A and tau were observed between 6 and 12 months of age. At 24 months the levels of MT-bound MAP2 and MAP1B decreased by 50% in contrast to MT-bound MAP1A levels which appeared to increase. The three high molecular weight MAPs but not tau rapidly degraded in the presence of calcium-activated endogenous proteases. No age-related changes in the rate of degradation were noted for the four cytoskeletal proteins. Levels of heat stable tau proteins but not heat stable MAP2 increased significantly with age.