Glutamine synthetase in cerebrospinal fluid, serum, and brain: a diagnostic marker for Alzheimer disease?

Abstract

OBJECTIVES:

To determine whether the glutamine synthetase (GS) level in cerebrospinal fluid (CSF) is a useful biochemical marker in the diagnosis of Alzheimer disease (AD), and to assess the source of GS (brain vs. blood derived) in CSF.

METHODS:

Sandwich enzyme immunoassay and immunoblotting were applied to detect GS in CSF and in serum from neurologically healthy control subjects and patients with neurodegenerative diseases, including AD. The origin of GS was estimated by the concentration gradients of CSF to serum and ventricular to lumbar CSF. In addition, postmortem brain tissue from controls and patients with AD was analyzed using immunohistochemistry for expression of GS.

RESULTS:

Levels of GS were significantly increased in lumbar CSF from patients with AD (20+/-12 pg/mL; P = .01) and to a lesser extent in patients with vascular dementia and amyotrophic lateral sclerosis. In CSF of controls, GS levels were 4+/-3 pg/mL. The GS concentration gradients were less than 1:10 for CSF to serum and 2:1 for ventricular to lumbar CSF. Immunoreactivity of GS was most prominent in astrocytes from temporal neocortex of patients with AD, suggesting a relationship between astrocyte reactions and increased GS levels in CSF.

CONCLUSIONS:

Level of GS in lumbar CSF of patients with AD is increased significantly but nonspecifically, probably related to the strong astrogliosis in brain. Glutamine synthetase in lumbar CSF is mainly brain derived.

• Authors: H Tumani, G Shen, J B Peter, W Brück
• Journal: Archives of neurology (Arch Neurol) Vol. 56 Issue 10 Pg. 1241-6 (Oct 1999) ISSN: 0003-9942 [Print] United States
• PMID: 10520940 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Glutamate-Ammonia Ligase

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Alzheimer Disease (blood, cerebrospinal fluid, diagnosis)
• Astrocytes (enzymology)
• Biomarkers
• Blotting, Western
• Brain (enzymology)
• Cerebrospinal Fluid (enzymology)
• Chemistry, Clinical (standards)
• Female
• Glutamate-Ammonia Ligase (analysis, blood, cerebrospinal fluid)
• Humans
• Immunoenzyme Techniques (standards)
• Immunohistochemistry
• Male
• Middle Aged
• Reference Values