Amino acid concentrations in cerebrospinal fluid and serum in Alzheimer's disease and vascular dementia

  • M. Martinez
  • A. Frank
  • E. Diez-Tejedor
  • A. Hernanz
Full Papers


Cerebrospinal fluid (CSF) and serum levels of 22 amino acids were studied in 13 patients with dementia of the Alzheimer type (DAT), 13 patients with vascular dementia (VD) and 15 age-matched controls. We found significantly reduced levels of glutamate in CSF samples from DAT patients compared to VD and control subjects, but CSF levels of aspartate were found to be significantly elevated in the two groups of dementia studied. Moreover, CSF concentrations of tyrosine, leucine and phenylalanine were significantly increased in VD patients in comparison with those in DAT patients and control subjects. Our results showed a wide increase in CSF/serum amino acid ratios in DAT and VD groups compared to controls. However, no differences were found in CSF/serum ratios between dementia groups. These changes show evidence for a possible disorder of amino acid metabolism with different patterns in these two dementia types.


Alzheimer's disease vascular dementia CSF amino acids aspartate glutamate 


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  1. Adolfsson R, Bucht G, Lithner F, Winblad B (1980) Hypoglycemia in Alzheimer's disease. Acta Med Scand 208: 387–388Google Scholar
  2. Antuono PG, Lehmann J, Koller KJ, Whitehouse PJ, Clark AW, Struble RG, Price DL, Baltimore JTC (1984) Endogenous neurotransmitter amino acids (ENNAA) in Alzheimer's disease (AD). Neurology 34 [Suppl 1]: 119Google Scholar
  3. Basun H, Forssell LG, Almkvist O, Cowburn RF, Eklöf R, Winblad B, Wetterberg L (1990) Amino acid concentrations in cerebrospinal fluid and plasma in Alzheimer's disease and healthy control subjects. J Neural Transm [P-D Sect] 2: 295–304Google Scholar
  4. Butcher SP, Sandberg M, Hagberg H, Hamberger A (1987) Cellular origins of endogenous amino acids released into the extracellular fluid of the rat striatum during severe insulin-induced hypoglycemia. J Neurochem 48: 722–728Google Scholar
  5. Clarke DD, Lajtha AL, Marker HS (1989) Intermediary metabolism. In: Siegel G, Agranoff BW, Albers RW, Molinoff PB (eds) Basic neurochemistry 4th ed. Raven Press, New York, pp 541–564Google Scholar
  6. Cohen SA, Bidlingmeyer BA, Tarvin TL (1986) PITC derivatives in amino acid analysis. Nature 320: 769–770Google Scholar
  7. Degrell I, Hellsing K, Nagy E, Niklasson F (1989) Amino acid concentrations in cerebrospinal fluid in presenile and senile dementia of Alzheimer type and multiinfarct dementia. Arch Gerontol Geriatr 9: 123–135Google Scholar
  8. Goldberg MP, Monyer H, Choi DW (1988) Hypoxic neuronal injury in vitro depends on extracellular glutamine. Neurosci Lett 94: 52–57Google Scholar
  9. Greenamyre JT (1986) The role of glutamate in neurotransmission and in neurologic disease. Arch Neurol 43: 1058–1063Google Scholar
  10. Greenamyre JT, Penney JB, D'Amato CJ, Young AB (1987) Dementia of the Alzheimer's type: changes in hippocampal L-(3H) glutamate binding. J Neurochem 48: 543–551Google Scholar
  11. Hayashi T (1954) Effects of sodium glutamate on the nervous system. Keio J Med 3: 183–192Google Scholar
  12. Hernanz A, Polanco I (1991) Plasma precursor amino acids of central nervous system monoamines in children with coeliac disease. Gut 32: 1478–1481Google Scholar
  13. Hoyer S, Nitsch R (1989) Cerebral excess release of neurotransmitter amino acids subsequent to reduced cerebral glucose metabolism in early-onset dementia of Alzheimer type. J Neural Transm 75: 227–232Google Scholar
  14. Kowall NW, Beal MF (1991) Glutamate-, glutaminase-, and taurine-immunoreactive neurons develop neurofibrillary tangles in Alzheimer's disease. Ann Neurol 29: 162–167Google Scholar
  15. Lowe SL, Bowen DM, Francis PT, Neary D (1990) Ante mortem cerebral amino acid concentrations indicate selective degeneration of glutamate-enriched neurons in Alzheimer's disease. Neuroscience 38: 571–577Google Scholar
  16. McGale EHF, Pye IF, Stoiner C, Hutchinson EC, Aber GM (1977) Studies of the interrelationship between cerebrospinal fluid and plasma amino acid concentrations in normal individuals. J Neurochem 29: 291–297Google Scholar
  17. Meldrum B (1985) Excitatory amino acids and anoxic/ischemic brain damage. Trends Neurosci 8: 47–48Google Scholar
  18. Parnetti L, Mecocci P, Santucci C, Gaiti A, Petrini A, Longo A, Cadini D, Caputo N, Signorini E, Senin U (1990) Is multi-infarct dementia representative of vascular dementias? A retrospective study. Acta Neurol Scand 81: 484–487Google Scholar
  19. Pomara N, Singh R, Deptula D, Chou JCY, Schwartz MB, Witt PAL (1992) Glutamate and other CSF amino acids in Alzheimer's disease. Am J Psychiatry 149: 251–254Google Scholar
  20. Procter AW, Palmer AM, Francis PT, Lowe SL, Neary D, Murphy E, Doshi R, Bowen DM (1988) Evidence of glutamatergic denervation and possible abnormal metabolism in Alzheimer's disease. J Neurochem 50: 790–802Google Scholar
  21. Schmitt L, Escando M, Gayral LF, Charlet JP, Thouvenot JP (1984) Anomalies des acides aminés du liquide céphalo-rachidien des demences séniles. J Psychiatr Biol Thér 16: 13–16Google Scholar
  22. Sims NR, Blass JP, Murphry C, Bowen BM, Neary D (1987) Phosphofructokinase activity in the brain in Alzheimer's disease. Ann Neurol 21: 509–510Google Scholar
  23. Smith CCT, Bowen DM, Francis PT, Snowden JS, Neary D (1985) Putative amino acid transmitters in lumbar cerebrospinal fluid of patients with histologically verified Alzheimer's disease. J Neurol Neurosurg Psychiatry 47: 469–471Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • M. Martinez
    • 1
  • A. Frank
    • 2
  • E. Diez-Tejedor
    • 2
  • A. Hernanz
    • 1
  1. 1.Department of BiochemistryHospital La PazMadridSpain
  2. 2.Department of NeurologyHospital La PazMadridSpain

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