Indoleamine 2,3 dioxygenase and quinolinic acid Immunoreactivity in Alzheimer's disease hippocampus

doi:10.1111/j.1365-2990.2005.00655.x

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Wiley InterScience

Neuropathology and Applied Neurobiology

Volume 31 Issue 4, Pages 395 - 404

Published Online: 25 May 2005

2007 Blackwell Publishing Ltd

Journal of the British Neuropathological Society

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Indoleamine 2,3 dioxygenase and quinolinic acid Immunoreactivity in Alzheimer's disease hippocampus

G. J. Guillemin*, B. J. Brew*†, C. E. Noonan‡, O. Takikawa§ and K. M. Cullen‡

*Centre for Immunology and †Department of Neurology, St Vincent's Hospital, Darlinghurst , ‡Department of Anatomy and Histology, The University of Sydney, Institute for Biomedical Research, Sydney, NSW, Australia , §Department of Molecular Biochemistry, Central Research Institute, School of Medicine, Hokkaido University, Sapporo, Japan

Correspondence to Dr K. M. Cullen, Department of Anatomy and Histology, Anderson Stuart Building F13, University of Sydney, NSW 2006 Australia. Tel: +61 2 9351 2696; Fax: +61 2 9351 2813; E-mail: kcullen@anatomy.usyd.edu.au

KEYWORDS

Alzheimer's disease • indoleamine 2,3 dioxygenase • kynurenine pathway • neurofibrillary tangles • neuroinflammation • quinolinic acid • senile plaques

G. J. Guillemin, B. J. Brew, C. E. Noonan, O. Takikawa and K. M. Cullen (2005) Neuropathology and Applied Neurobiology31, 000–000
Indoleamine 2,3 dioxygenase and quinolinic acid Immunoreactivity in Alzheimer's disease hippocampus

ABSTRACT

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.

Received 10 August, 2004 Accepted after revision 10 February 2005

DIGITAL OBJECT IDENTIFIER (DOI)

10.1111/j.1365-2990.2005.00655.x About DOI