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Advanced Glycation End Products In Alzheimer’s Disease And Other Neurodegenerative Diseases

Source: American Journal of Pathology. 1998;153:1149-1155
Authors: Nobuyuki Sasaki, Ryo Fukatsu, Kayo Tsuzuki, Yorihide Hayashi, Taku Yoshida, Nobuhiro Fujii, Takao Koike, Ikuro Wakayama, Richard Yaoagihara, Ralph Garruto, Naoji Amuno, and Zemji Makita

Advanced glycation end products (AGEs) have been implicated in the chronic complications of diabetes mellitus and have been reported to play an important role in the pathogenesis of Alzheimer’s disease. In this study, we examined the immunohistochemical localization of AGEs, amyloid B protein (AB), apolipoprotein E (ApoE), and tau protein in senile plaques, neurofibrillary tangles (NFTs), and cerebral amyloid angiopathy (CAA) in Alzheimer’s disease and other neurodegenerative diseases (progressive supranuclear palsy, Pick’s disease, and Guamanian amyotrophic lateral sclerosis/Parkinsonism-dementia complex). In most senile plaques (including diffuse plaques) and CAA from Alzheimer’s brains, AGE and ApoE were observed together. However, approximately 5% of plaques were AGE positive but AB negative, and the vessels without CAA often showed AGE immunoreactivity. In Alzheimer’s disease, AGEs were mainly present in intracellular NFTs, whereas ApoE was mainly present in extracellular NFTs. Pick’s bodies in Pick’s disease and granulovacuolar degeneration in various neurodegenerative disease were also AGE positive. In non-Alzheimer neurodegernerative diseases, senile plaques and NFT showed similar findings to those in Alzheimer’s disease. These results suggest that AGE may contribute to eventual neuronal dysfunction and death as an important factor in the progression of various neurodegenerative disease, including Alzheimer’s disease.

Authors from the Departments of Neuropsychiatry and Microbiology. Sapporo Medical University, Sapporo, the Second Department of Medicine, Hokkaido University, Sapporo, the Kansai College of Oriental Medicine, Osaka, Japan, and the Department of Neuropsychiatry, Tokyo University, Tokyo, Japan, and Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.