Indoleamine 2,3 dioxygenase and quinolinic acid immunoreactivity in Alzheimer's disease hippocampus.
The present immunohistochemical study provides evidence that the kynurenine pathway is up-regulated in Alzheimer's disease (AD) brain, leading to increases in the excitotoxin quinolinic acid (QUIN). We show that the regulatory enzyme of the pathway leading to QUIN synthesis, indoleamine 2,3 dioxygenase (IDO) is abundant in AD compared with controls. In AD hippocampus, both IDO- and QUIN-immunoreactivity (-IR) was detected in cortical microglia, astrocytes and neurones, with microglial and astrocytic expression of IDO and QUIN highest in the perimeter of senile plaques. QUIN-IR was present in granular deposits within the neuronal soma of AD cortex and was also seen uniformly labelling neurofibrillary tangles. Our data imply that QUIN may be involved in the complex and multifactorial cascade leading to neuro-degeneration in AD. These results may open a new therapeutic door for AD patients.
Guillemin
G J
GJ
Centre for Immunology, St Vincent's Hospital, Darlinghurst, NSW, Australia.
Brew
B J
BJ
Noonan
C E
CE
Takikawa
O
O
Cullen
K M
KM
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism; D017378:Quinolinic Acid / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000378:metabolism*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014366:Tryptophan Oxygenase; D017378:Quinolinic Acid