Localization of identified advanced glycation end-product structures, N epsilon(carboxymethyl)lysine and pentosidine, in age-related inclusions in human brains.
The recent identification of age-related accumulation of advanced glycation end-products (AGE) of the Maillard reaction in neurons and vessels of the human brain suggests the involvement of AGE in the aging process. A variety of inclusions such as lipofuscin granules, corpora amylacea, Hirano bodies, granulovacuolar degenerations and ubiquitin-positive granular structures are found in the aged human brain. These age-related inclusions contain insoluble and non-degradable proteins. Advanced glycation end-product-modified proteins are also known to be insoluble and protease resistant. The similarity between proteins in such inclusions and AGE-modified proteins suggests the presence of AGE in inclusions. To investigate this possibility, the presence of two known AGE structures, N epsilon(carboxymethyl)lysine (CML) and pentosidine, was examined in age-related inclusions. Immunohistochemical examination of the medial temporal area of brain tissues obtained at autopsy from seven non-demented elderly individuals demonstrated positive reactions in lipofuscin granules and corpora amylacea but not in other inclusions for anti-CML and anti-pentosidine antibodies. As CML and pentosidine are glycoxidation products among AGE, the results suggest that glycation and/or oxidation may be involved in the formation of lipofuscin granules and corpora amylacea.
Kimura
T
T
Department of Neuropsychiatry, Kumamoto University School of Medicine, Japan. tkimura@kaiju.medic.kumamoto-u.ac.jp
Takamatsu
J
J
Miyata
T
T
Miyakawa
T
T
Horiuchi
S
S
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D018728:Entorhinal Cortex / Q000378:metabolism / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D002479:Inclusion Bodies / Q000378:metabolism* / Q000473:pathology; D008062:Lipofuscin / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D015416:Maillard Reaction; D008875:Middle Aged; D014452:Ubiquitins / Q000378:metabolism
D017127:Glycation End Products, Advanced; D008062:Lipofuscin; D014452:Ubiquitins; C048496:N(6)-carboxymethyllysine; D001120:Arginine; C062187:pentosidine; D008239:Lysine