Glutamine synthetase in cerebrospinal fluid, serum, and brain - A diagnostic marker for Alzheimer disease?

Objectives: To determine whether the glutamine synthetase (GS) level in cer ebrospinal fluid (CSF) is a useful biochemical marker in the diagnosis of a lzheimer disease (AD), and to assess the source of GS (brain vs blood deriv ed) in CSF. Methods: Sandwich enzyme immunoassay and immunoblotting were applied to det ect GS in CSF and in serum from neurologically healthy control subjects and patients with neurodegenerative diseases, including AD. The origin of GS w as estimated by the concentration gradients of CSF to serum and ventricular to lumbar CSF. In addition, postmortem brain tissue from controls and pati ents with AD was analyzed using immunohistochemistry for expression of GS. Results: Levels of GS were significantly increased in lumbar CSF from patie nts with AD (20 +/- 12 pg/mL; P=.01) and to a lesser extent in patients wit h 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. Immunoreactiv ity of GS was most prominent in astrocytes from temporal neocortex of patie nts with AD, suggesting a relationship between astrocyte reactions and incr eased GS levels in CSF. Conclusions: Level of GS in lumbar CSF of patients with AD is increased sig nificantly but nonspecifically, probably related to the strong astrogliosis in brain. Glutamine synthetase in lumbar CSF is mainly brain derived.