Glycation and microglial reaction in lesions of Alzheimer's disease.
Single, double, and triple immunostaining of cryostat sections of elderly normal and Alzheimer disease (AD) brain was performed with monoclonal and polyclonal antibodies to advanced glycation end products (AGE). The sections were counterstained with thioflavin-S or with immunocytochemistry for A beta and also stained with markers for microglia. AGE-immunoreactivity was detected in senile plaques and neurofibrillary tangles (NFT). AGE immunoreactivity was most intense in dense or reticular amyloid deposits and extracellular NFT, while intracellular NFT and diffuse amyloid had less AGE immunoreactivity. This pattern of immunoreactivity was similar to that noted in previous studies with antibodies to apolipoprotein-E (apo-E). Therefore, double labeling with antibodies to apo-E and AGE was performed. AGE immunoreactivity colocalized to a very high degree with apo-E immunoreactivity, except that relatively more intense apo-E immunoreactivity was detected in amyloid deposits and more intense AGE immunoreactivity in NFT. The lesions that were immunostained with antibodies to AGE and apo-E were often, but not always, associated with a local microglial reaction. The results raise the possibility that apo-E or a fragment of apo-E may be glycated. Biochemical studies are needed to determine the extent of possible apo-E glycation in AD. The present results raise the possibility that glycation may serve as one of the signals for activation of microglia associated with amyloid deposits and extracellular NFT.
Dickson
D W
DW
Department of Pathology and Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Sinicropi
S
S
Yen
S H
SH
Ko
L W
LW
Mattiace
L A
LA
Bucala
R
R
Vlassara
H
H
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D001057:Apolipoproteins E / Q000378:metabolism; D001921:Brain / Q000473:pathology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000502:physiology*; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology
D001057:Apolipoproteins E; D017127:Glycation End Products, Advanced