The current study describes both Abeta and tau abnormalities that accumulate in the brains of aged (16-21 years), but not young (<4 years) clinically characterized cats. Diffuse plaques that were morphologically different from what is typically observed in the human brain could be detected with 4G8 (Abeta17-24) or an Abeta1-42-specific antibody but not with N-terminal Abeta or an Abeta1-40-specific antibody. SELDI-TOF mass spectrometry experiments indicated that cat brain Abeta consisted almost entirely of Abeta1-42. Markers of tau hyperphosphorylation (AT8 and PHF-1) labeled a subset of neurons in two aged animals. In the hilus of the hippocampus, a subset of AT8 positive neurons showed a sprouting morphology similar to that observed in human brain. Western blot analysis with antibodies against hyperphosphorylated tau indicated that tau is hyperphosphorylated in the aged cat and contains many of the same epitopes found in Alzheimer's disease (AD) brain. Thus, the aged cat brain develops AD-related lesions with important morphological and biochemical differences compared to human brain.