Advanced Maillard reaction end products are associated with Alzheimer disease pathology.
During aging long-lived proteins accumulate specific post-translational modifications. One family of modifications, termed Maillard reaction products, are initiated by the condensation between amino groups of proteins and reducing sugars. Protein modification by the Maillard reaction is associated with crosslink formation, decreased protein solubility, and increased protease resistance. Here, we present evidence that the characteristic pathological structures associated with Alzheimer disease contain modifications typical of advanced Maillard reaction end products. Specifically, antibodies against two Maillard end products, pyrraline and pentosidine, immunocytochemically label neurofibrillary tangles and senile plaques in brain tissue from patients with Alzheimer disease. In contrast, little or no staining is observed in apparently healthy neurons of the same brain. The Maillard-reaction-related modifications described herein could account for the biochemical and insolubility properties of the lesions of Alzheimer disease through the formation of protein crosslinks.
Smith
M A
MA
Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106.
Taneda
S
S
Richey
P L
PL
Miyata
S
S
Yan
S D
SD
Stern
D
D
Sayre
L M
LM
Monnier
V M
VM
Perry
G
G
D000544:Alzheimer Disease / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D015416:Maillard Reaction; D016874:Neurofibrillary Tangles / Q000378:metabolism; D009646:Norleucine / Q000031:analogs & derivatives* / Q000378:metabolism; D011758:Pyrroles / Q000378:metabolism*
D017127:Glycation End Products, Advanced; D011758:Pyrroles; C059571:2-formyl-5-(hydroxymethyl)pyrrole-1-norleucine; D009646:Norleucine; D001120:Arginine; C062187:pentosidine; D008239:Lysine