DISTRIBUTION OF ADVANCED GLYCATION END-PRODUCTS IN THE CEREBELLAR NEURONS OF DOGS

Nonenzymatically glycated proteins and their advanced stage, the 'adva nced glycation end products' (AGEs), have been detected in long-lived proteins and protein deposits in human and animal tissues. They are th ought to be associated with normal aging and particularly with the pat hogenesis of diabetic complications and Alzheimer's disease. AGEs accu mulate in human neurons in an age-dependent manner and, in Alzheimer's disease patients, particularly in amyloid plaques and neurofibrillary tangles. in this study, we demonstrate AGE immunoreactivity in the ca nine brain, particularly in cerebellar Purkinje cells and brainstem ne urons. Zn addition, distinct AGE-positive granules can be detected in the Purkinje cells which accumulate in an age-dependent manner. Staini ng with PAS and oil-red suggests that these AGE-positive granules cont ain the protein, but not the lipid constituents associated with lipofu scin. Our results show that the pattern of AGE distribution in the can ine cerebellum resembles the situation in the human brain, but that th e time course of AGE formation is much faster in dogs reflecting their much shorter life span. (C) 1998 Elsevier Science B.V.