Neurotransmitter amino acids in cerebrospinal fluid of patients with Alzheimer's disease

Abstract

We measured the CSF and plasma levels of glutamate, glutamine, aspartate (only in plasma), asparagine, glutamine, glycine and GABA in 37 patients with Alzheimer's disease and in 32 matched controls. We used an ion-exchange chromatography method. When compared to controls, AD patients had higher CSF glutamate and glycine levels, higher plasma levels of aspartate and glycine, and lower plasma levels of asparagine and GABA. When expressed relative to CSF proteins, CSF levels of glutamate and glycine remained higher, and CSF asparagine levels were lower in AD patients than in controls. The CSF levels of the amino acids measured were not correlated with the clinical features of AD with the exception of plasma GABA levels with duration of the disease. Our results might suggest a possible pathogenetic role of neurotransmitter amino acids in AD.

Ceftriaxone ameliorates tau pathology and cognitive decline via restoration of glial glutamate transporter in a mouse model of Alzheimer's disease

“…This effect can lead to glutamate dyshomeostasis and/or glutamate excitotoxicity. This phenomenon has been suggested in AD because AD patients have increasing glutamate levels in their cerebral spinal fluid as dementia progresses (Jimenez-Jimenez et al, 1998;Kaiser et al, 2010).…”

Memantine Blocks α7*Nicotinic Acetylcholine Receptors More Potently ThanN-Methyl-D-aspartate Receptors in Rat Hippocampal Neurons

“…This effect does not seem to result from a selective interaction of memantine with the NR2B-containing NMDA receptors that prevail in extrasynaptic compartments of central nervous system neurons (Tovar and Westbrook, 1999). Instead, the rapid blocking kinetics, in addition to the high voltage-and use-dependent NMDA receptor inhibition by memantine seem to favor the blockade of extrasynaptic NMDA receptors (Danysz and Parsons, 2003;Rogawski and Wenk, 2003) that are likely to be repetitively activated by the elevated extracellular levels of glutamate in the brain of AD patients (Jiménez-Jiménez et al, 1998).…”

Changes in the cellular distribution of glutamine synthetase in Alzheimer's disease

“…A substantial proportion of neurons in these regions are glutamatergic and a body of evidence indicates that some of the neurodegeneration in AD occurs as a result of glutamate excitotoxicity (Arias et al, 1998). This excitotoxicity is thought to result from a chronic elevation in the levels of glutamate in the extracellular space, and several research groups have confirmed that the levels of glutamate are significantly elevated in the cerebrospinal fluid of AD patients (Csernansky et al, 1996;Jimenez-Jimenez et al, 1998;Redjems-Bennani et al, 1998;Smith et al, 1985); see however (Basun et al, 1990). Although the cause of this elevation has not yet been determined, astrocytes appear to be implicated because the activity and expression of their glutamate uptake transporters are substantially reduced in AD (Lauderback et al, 2001;Li et al, 1997;Masliah et al, 1996).…”