Glyceraldehyde-derived advanced glycation end products in Alzheimer's disease.
The Maillard reaction that leads to the formation of advanced glycation end products (AGE) is considered to play an important role in the pathogenesis of Alzheimer's disease (AD). Until now AGE derived from glucose (glucose-AGE) have been mainly investigated, so we established new AGE species derived from alpha-hydroxyaldehydes and dicarbonyl compounds. We have found that AGE derived from glyceraldehyde (glycer-AGE) and glycolaldehyde (glycol-AGE) showed strong neurotoxicity for primary cultured rat cortical neurons in vitro. In this study, we immunohistochemically examined the localization of glycer-AGE and glycol-AGE in the brains of AD patients and elderly controls. Most of the neurons in AD or control brains did not show any immunoreaction with glycol-AGE. In AD brains, glycer-AGE was mainly present in the cytosol of neuron in the hippocampus and para-hippocampal gyrus, but not in senile plaques and astrocytes. The pattern of immunopositivity was uniform and powdery, not dot-like. The distribution of glycer-AGE differed from that of glucose-AGE, which was detected at both intracellular and extracellular sites. This suggests that glycer-AGE has a pathological role different from glucose-AGE in AD. In the central nervous system, glyceraldehyde is generated via the glycolytic pathway from glyceraldehyde-3-phosphate by glyceraldehyde-3-phosphate dehydrogenase (GAPDH). We hypothesize that perikaryal glycer-AGE immunopositivity of neurons reflects an increase of cytoplasmic glycer-AGE along with the decline of GAPDH activity.
Choei
Hiroshi
H
Department of Neuropsychiatry, Sapporo Medical University School of Medicine, Sapporo, Japan.
Sasaki
Nobuyuki
N
Takeuchi
Masayoshi
M
Yoshida
Taku
T
Ukai
Wataru
W
Yamagishi
Sho-Ichi
S
Kikuchi
Seiji
S
Saito
Toshikazu
T
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000378:metabolism*; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D005985:Glyceraldehyde / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D015416:Maillard Reaction; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology
D017127:Glycation End Products, Advanced; D005985:Glyceraldehyde; D000079:Acetaldehyde; C010972:glycolaldehyde