Detection of N epsilon-(carboxymethyl)lysine (CML) and non-CML advanced glycation end-products in the anterior horn of amyotrophic lateral sclerosis spinal cord.
BACKGROUND
The involvement of glycation in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS) was recently indicated. We previously reported the existence of an Amadori product, 1-hexitol-lysine (1-HL), which is formed in the early glycation reaction, in axonal spheroids of the anterior horn of the ALS spinal cord.


OBJECTIVE
The purpose of the present study was to confirm the occurrence of the later-stage glycation reaction that follows the early glycation reaction and leads to the formation of advanced glycation end products (AGEs).


METHODS
We examined whether N(epsilon)-(carboxymethyl)lysine (CML) and non-CML AGE are present in ALS spinal cords.


RESULTS
Immunohistochemical staining with anti-CML antibody revealed intense positivity in the cell bodies of the remaining atrophic motor neurons and in microglia. Microglia were also positive on staining with anti-non-CML antibody. Axonal spheroids were also positive on anti-non-CML-antibody staining. Vascular endothelial cells were slightly stained by both antibodies.


CONCLUSIONS
The presence of non-CML AGE in the anterior horn of the ALS spinal cord indicates that the later stage of the glycation reaction is involved in the pathology of ALS. The presence of CML in the anterior horn was also confirmed, and this may reflect augmented oxidative stress.
Kikuchi
Seiji
S
Department of Neurology, Hokkaido University School of Medicine, Sapporo, Japan. skikuti@med.hokudai.ac.jp
Shinpo
Kazuyoshi
K
Ogata
Akihiko
A
Tsuji
Sachiko
S
Takeuchi
Masayoshi
M
Makita
Zenji
Z
Tashiro
Kunio
K
D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D001344:Autopsy; D001369:Axons / Q000737:chemistry; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000737:chemistry / Q000473:pathology; D013116:Spinal Cord / Q000737:chemistry* / Q000473:pathology
D017127:Glycation End Products, Advanced; C048496:N(6)-carboxymethyllysine; D008239:Lysine