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N-Acetyl Aspartic Acid (NAA) and N-Acetyl Aspartylglutamic Acid (NAAG) in Human Ventricular,Subarachnoid, and Lumbar Cerebrospinal Fluid
Authors:Faull  Kym F.  Rafie  Ramin  Pascoe  Nina  Marsh  Laura  Pfefferbaum  Adolf
Affiliation:(1) Pasarow Mass Spectrometry Laboratory, Departments of Chemistry & Biochemistry and Psychiatry & Biobehavioral Sciences and the Neuropsychiatric Institute, UCLA, Los Angeles, CA, 90095;(2) Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305;(3) Department of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287;(4) Neuropsychiatry Program, SRI International, Menlo Park, CA, 94025;(5) Department of Chemistry & Biochemistry, UCLA, Los Angeles, 90095
Abstract:N-Acetylaspartic and N-acetylaspartylglutamic acid concentrations in human ventricular, subarachnoid and lumbar cerebrospinal fluid were measured by combined gas chromatography-mass spectrometry using selected ion monitoring with deuterated internal standards. N-Acetylaspartate concentrations were in the range 55, 9, and 1 mgrM, respectively; N-acetylaspartylglutamate concentrations in the same fluids were in the range 8, 3 and 4 mgrM, respectively. There did not appear to be any difference in lumbar fluid concentrations of either compound between control subjects, schizophrenic patients, Alzheimer's disease patients and a pooled group of patients with neurological degeneration. Ventricular concentrations of both compounds were greatly increased in deceased patients suggesting that maintenance of their intracellular concentrations is probably energy dependent. The concentrations of these compounds in lumbar cerebrospinal fluid from living, and ventricular cerebrospinal fluid from deceased subjects were weakly correlated with one another. In lumbar fluid neither compound appeared to be correlated with age. Analysis of serially collected lumbar samples from two subjects showed a weak concentration gradient for both compounds. Neither antipsychotic medication nor the acid transport inhibitor probenecid had any effect on lumbar concentrations of either compound. Attempts to use anion exchange high pressure liquid chromatography with UV detection for measurement of the low concentrations of N-acetylaspartate found in cerebrospinal fluid from living subjects were unsuccessful.
Keywords:N-Acetylaspartic acid  N-acetylaspartylglutamic acid  cerebrospinal fluid  CSF  neuronal degeneration  HPLC  GC/MS
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