Amino acid concentrations in cerebrospinal fluid and plasma in Alzheimer's disease and healthy control subjects (original) (raw)
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Amino acid concentration in dementia of the Alzheimer type and multi-infarct dementia
Annals of clinical and laboratory science
Amino acids were measured in nine cases of dementia of the Alzheimer type, 10 cases of multi-infarct dementia, and 10 healthy controls. The severity of dementia was examined using mini-mental state test (MMST). Amino acid analysis (41 kinds) in the cerebrospinal fluid (CSF) and serum was performed in the Special Reference Laboratories. In the dementia of the Alzheimer type group, methionine and alanine concentrations in the CSF were significantly increased, and the CSF/serum ratios for both the alanine and glycine concentrations were significantly increased, in comparison with the healthy control group. In the multi-infarct dementia group, glycine, methionine, threonine, phenylalanine, and citrulline concentrations in the CSF were all higher than in the healthy control group. Significant negative correlations were found between the MMST score and the alanine, urea, arginine, and alpha-aminobutyric acid concentrations in the CSF. The number of amino acids which exhibited abnormality ...
Alzheimer’s disease: amino acid levels and brain metabolic status
Neurological Sciences, 2013
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Serum Amino Acid Profiles in Normal Subjects and in Patients with or at Risk of Alzheimer Dementia
Dementia and Geriatric Cognitive Disorders Extra
Background/Aims: Abnormalities in the plasma amino acid profile have been reported in Alzheimer disease (AD), but no data exist for the prodromal phase characterized by subjective memory complaint (SMC). It was our aim to understand if serum amino acid levels change along the continuum from normal to AD, and to identify possible diagnostic biomarkers. Methods: Serum levels of 15 amino acids and 2 organic acids were determined in 4 groups of participants-29 with probable AD, 18 with mild cognitive impairment (MCI), 24 with SMC, and 46 cognitively healthy subjects (HS)-by electrospray tandem mass spectrometry. Results: Glutamate, aspartate, and phenylalanine progressively decreased, while citrulline, argi ninosuccinate, and homocitrulline progressively increased, from HS over SMC and MCI to AD. The panel including these 6 amino acids and 4 ratios (glutamate/citrulline, citrulline/phenyl alanine, leucine plus isoleucine/phenylalanine, and arginine/phenylalanine) discriminated AD from HS with about 96% accuracy. Other panels including 20 biomarkers discriminated SMC or MCI from AD or HS with an accuracy ranging from 88 to 75%. Conclusion: Amino acids contribute to a characteristic metabotype during the progression of AD along the continuum from health to frank dementia, and their monitoring in elderly individuals might help to detect atrisk subjects.
Free D- and L-amino acids in ventricular cerebrospinal fluid from Alzheimer and normal subjects
Amino Acids, 1998
Free D-Ser, D-Asp and total D-amino acids were significantly higher (p < 0.05) in Alzheimer (AD) ventricular CSF than in normal CSF. There was no significant difference in the total L-amino acids between AD and normal CSF, but L-GIn and L-His were significantly higher (p < 0.05) in AD-CSF. The higher concentrations of these D-and L-amino acids in AD ventricular CSF could reflect the degenerative process that occurs in Alzheimer's brain since ventricular CSF is the repository of amino acids from the brain.
Alzheimer's & Dementia, 2013
Background: Behavioral and psychological signs and symptoms of dementia (BPSD) are a heterogeneous group of behavioral and psychiatric disturbances occurring in dementia patients of any etiology. Research suggests that altered activities of dopaminergic, serotonergic, (nor)adrenergic, as well as amino acid neurotransmitter systems play a role in the etiopathogenesis of BPSD. In this study we attempted to identify cerebrospinal fluid (CSF) neurochemical correlates of BPSD to provide further insight into its underlying neurochemical pathophysiological mechanisms. Methods: Patients with probable Alzheimer's disease (AD; n 5 202), probable AD with cerebrovascular disease (n 5 37), probable frontotemporal dementia (FTD; n 5 32), and probable dementia with Lewy bodies (DLB; n 5 26) underwent behavioral assessment and lumbar puncture. CSF levels of six amino acids and several biogenic amines and metabolites were analyzed using ultraperformance liquid chromatography with fluorescence detection and reversed-phase high-performance liquid chromatography with fluorescence detection. Results: In the AD patients, CSF homovanillic acid/5-hydroxyindoleacetic acid (HVA/5HIAA) ratios correlated positively with anxieties/phobias, whereas CSF levels of taurine correlated negatively with depression and behavioral disturbances in general. In FTD patients, CSF levels of glutamate correlated negatively with verbally agitated behavior. In DLB patients, CSF levels of HVA correlated negatively with hallucinations. Conclusions: Several neurotransmitter systems can be linked to one specific behavioral syndrome depending on the dementia subtype. In addition to biogenic amines and metabolites, amino acids seem to play a major role in the neurochemical etiology of BPSD as well.
Neurotransmitter amino acid in cerebrospinal fluid of patients with dementia with Lewy bodies
Journal of Neural Transmission, 2005
The purpose of the present study was to compare neurotransmitter amino acid concentrations in the cerebrospinal fluid (CSF) and CSF/plasma ratios in 21 patients with dementia with Lewy bodies (DLB) and 26 matched controls. To this purpose, we used an ion-exchange chromatographic method. DLB patients exhibit higher CSF concentrations of asparagine (+25%) and glycine (+21%) compared to a control group, whereas no differences in CSF/plasma ratios were found between both groups. On the other hand, no alterations in concentrations of glutamate, aspartate and GABA were detected in CSF of patients compared to a control group. There was no correlation among amino acid levels and CSF/plasma ratios with age, age of onset, body mass index, duration of the disease or scores of the Mini Mental State Examination, UPDRS and Hoehn and Yahr stage. These results suggest a possible role of glycine and asparagine in the pathogenic mechanism of dementia with Lewy bodies.
Evidence of Glutamatergic Denervation and Possible Abnormal Metabolism in Alzheimer's Disease
Journal of Neurochemistry, 1988
Excitatory dicarboxylic amino acids previously have been ascribed several functions in the brain. Here their total concentration and proposed neurochemical markers of neurotransmitter function have been measured in brain from patients with Alzheimer's disease (AD) and controls. Specimens were obtained antemortem (biopsy) approximately 3 years after emergence of symptoms and promptly (<3 h) postmortem some 10 years after onset. Early in the disease a slight elevation in aspartic acid concentration of cerebral cortex was observed in the patients with AD. A reduction in glutamic acid concentration of a similar magnitude was found. It is argued that this, together with a decrease in CSF glutamine content and lack of change in the phosphate-activated brain glutaminase activity of tissue, reflects an early metabolic abnormality. Later in the disease evidence of glutamatergic neurone loss is provided by the finding that in many regions of the cerebral cortex the Na+-dependent uptake of D-[3H]aspartic acid was almost always lowest in AD subjects compared with control when assessed by a method designed to minimise artifacts and epiphenomena. Release of endogenous neuro-transmitters from human brain tissue postmortem did not appear to have the characteristics of that from human tissue antemortem and rat brain.
Nutrients
Conflicting results about alterations of plasma amino acid (AA) levels are reported in subjects with Alzheimer’s disease (AD). The current study aimed to provide more homogeneous AA profiles and correlations between AAs and cognitive tests. Venous plasma AAs were measured in 54 fasting patients with AD (37 males, 17 females; 74.63 ± 8.03 yrs; 3.2 ± 1.9 yrs from symptom onset). Seventeen matched subjects without neurodegenerative symptoms (NNDS) served as a control group (C-NNDS). Patients were tested for short-term verbal memory and attention capacity and stratified for nutritional state (Mini Nutritional Assessment, MNA). Compared to C-NNDS, patients exhibited lower plasma levels of aspartic acid and taurine (p < 0.0001) and higher 3-methylhistidine (p < 0.0001), which were independent of patients’ MNA. In comparison to normonourished AD, the patients at risk of and with malnutrition showed a tendency towards lower ratios of Essential AAs/Total AAs, Branched-chain AAs/Total A...