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Free amino acid and dipeptide changes in the body fluids from Alzheimer’s disease subjects

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Summary.

Our aim was to determine changes in free amino acid (FAA) and dipeptide (DP) concentrations in probable Alzheimer’s disease (pAD) subjects compared with control (CT) subjects using liquid chromatography and electrospray ionization tandem mass spectrometry (LCMS2). We recruited gender- and age-matched study participants based on neurological and neuropsychological assessments. We measured FAAs and DPs in cerebrospinal fluid (CSF), plasma and urine using LCMS2 with selected reaction monitoring (SRM). Imidazole-containing FAAs (histidine, methyl-histidine), catecholamines (L-DOPA and dopamine), citrulline, ornithine, glycine and antioxidant DPs (carnosine and anserine) accounted for the major changes between CT and pAD. Carnosine levels were significantly lower in pAD (328.4 ± 91.31 nmol/dl) than in CT plasma (654.23 ± 100.61 nmol/dl). In contrast, L-DOPA levels were higher in pAD (1400.84 ± 253.68) than CT (513.10 ± 121.61 nmol/dl) plasma. These data underscore the importance of FAA and DP metabolism in the pathogenesis of AD. Since our data show changes in antioxidants, neurotransmitters and their precursors, or FAA associated with urea metabolism in pAD compared with CT, we propose that manipulation of these metabolic pathways may be important in preventing AD progression.

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Abbreviations

CT:

control study participants

pAD:

probable Alzheimer’s disease study participants

CT_M:

control male

CT_F:

control female

pAD_M:

pAD male

pAD_F:

pAD female

MMSE:

mini-mental state examination

ADAS-cog:

Alzheimer’s Disease Assessment Scale- cognitive subscale

LCMS2 :

liquid chromatography electrospray ionization tandem mass spectrometry

SRM:

selected reaction monitoring

FAA:

free amino acid

DP:

dipeptide

GABA:

γ-aminobutyric acid

βABA:

β-aminobutyric acid

ABA:

α-aminobutyric acid

DABA:

2,4-diaminobutyric acid

DOPA:

3,4-dihydroxyphenyl-L-alanine

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  1. Molecular Neurology Program, Huntington Medical Research Institutes, Pasadena, CA, U.S.A.

    A. N. Fonteh, R. J. Harrington, A. Tsai, P. Liao & M. G. Harrington

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  1. A. N. Fonteh
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  3. A. Tsai
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  4. P. Liao
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Fonteh, A., Harrington, R., Tsai, A. et al. Free amino acid and dipeptide changes in the body fluids from Alzheimer’s disease subjects. Amino Acids 32, 213–224 (2007). https://doi.org/10.1007/s00726-006-0409-8

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