Free and conjugated amino acids in human CSF: Influence of age and sex

Abstract

An extended baseline characterization of amino acids (AAs) and related amino compounds in CSF is reported. Thirty-one amino compounds were measured in deproteinized CSF before and after acid hydrolysis using a triple-column HPLC/fluorometric analyzer. CSF specimens were collected under strictly controlled conditions from neurologically normal myelogram patients and carefully pooled with regard to subject age and sex. Consideration was given to factors which may produce artifactual alterations in AA levels during CSF collection, storage and handling. Conjugated AAs were determined as the difference between levels of free AAs (measured in CSF prior to hydrolysis) and total AAs (measured in hydrolyzed CSF) and are taken as an index of total CSF peptide AAs. Results documented conjugated forms of all non-acid-labile CSF AAs except citrulline and ethanolamine. In general, ratios of conjugated to free AAs were relatively low, however for the neurotransmitter AAs aspartate, glutamate, glycine and GABA as well as for β-alanine hydrolysis produced marked increases indicating that these compounds are present predominantly in bound form in CSF. Results also revealed the significant influence of both age and sex on levels of a number of CSF free and conjugated AAs. Compared to younger individuals (those less than 40 years of age), older individuals exhibited significantly higher levels of free aspartate, glycine, α-aminobutyric acid, valine, isoleucine, leucine, phenylalanine and 3-methylhistidine as well as significantly lower levels of free phosphoethanolamine, serine, GABA, homocarnosine, conjugated GABA and conjugated β-alanine. Additionally, significantly higher levels of free tyrosine, ethanolamine, arginine and conjugated aspartate were documented in males compared to females. Thus, the careful approach to data collection has facilitated a baseline characterization of CSF peptide AAs as well as an extended characterization of CSF free AAs documenting the significant influence of age and sex. Results further support the view that CSF neurochemical measurements can be useful for studying CNS function only when appropriate consideration is given to variables which may influence results.