CSF d-serine concentrations are similar in Alzheimer's disease, other dementias, and elderly controls

Biemans, Elisanne A.L.M.; Verhoeven‐Duif, Nanda M.; Gerrits, Johan; Claassen, Jurgen A.H.R.; Kuiperij, H. Bea; Verbeek, Marcel M.

doi:10.1016/j.neurobiolaging.2016.03.017

Cited by 44 publications

(25 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another group indicated that there was no statistically significant difference in serine concentration between the CSF of patients with AD and that of controls [ 14 , 45 ]. However, these studies were performed with relatively small sample sizes and amino acids concentration in the CSF seemingly influenced by the content of daily diet [ 46 ], further studies with larger sample sizes are needed to elucidate the relations between serine concentration in the CSF and AD.…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of cerebrospinal fluid metabolites in Alzheimer’s disease and idiopathic normal pressure hydrocephalus in a Japanese cohort

et al. 2018

View full text Add to dashboard Cite

BackgroundAlzheimer’s disease (AD) is a most common dementia in elderly people. Since AD symptoms resemble those of other neurodegenerative diseases, including idiopathic normal pressure hydrocephalus (iNPH), it is difficult to distinguish AD from iNPH for a precise and early diagnosis. iNPH is caused by the accumulation of cerebrospinal fluid (CSF) and involves gait disturbance, urinary incontinence, and dementia. iNPH is treatable with shunt operation which removes accumulated CSF from the brain ventricles.MethodsWe performed metabolomic analysis in the CSF of patients with AD and iNPH with capillary electrophoresis-mass spectrometry. We assessed metabolites to discriminate between AD and iNPH with Welch’s t-test, receiver operating characteristic (ROC) curve analysis, and multiple logistic regression analysis.ResultsWe found significant increased levels of glycerate and N-acetylneuraminate and significant decreased levels of serine and 2-hydroxybutyrate in the CSF of patients with AD compared to the CSF of patients with iNPH. The ROC curve analysis with these four metabolites showed that the area under the ROC curve was 0.90, indicating good discrimination between AD and iNPH.ConclusionsThis study identified four metabolites that could possibly discriminate between AD and iNPH, which previous research has shown are closely related to the risk factors, pathogenesis, and symptoms of AD. Analyzing pathway-specific metabolites in the CSF of patients with AD may further elucidate the mechanism and pathogenesis of AD.Electronic supplementary materialThe online version of this article (10.1186/s40364-018-0119-x) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Comparative analysis of cerebrospinal fluid metabolites in Alzheimer’s disease and idiopathic normal pressure hydrocephalus in a Japanese cohort

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Elevated Glu concentrations were also detected in CSF samples from patients with AD, however no correlation between this increase and clinical features was identified [10,11]. Observations about CSF levels of other AAs during AD are more contradictory [10][11][12][13][14]. Taken together, these numerous observations confirm that knowledge about the regulatory mechanisms underlying the maintenance of CSF AA homeostasis is important and relevant for clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Choroid plexus LAT2 and SNAT3 as partners in CSF amino acid homeostasis maintenance

Dolgodilina

Camargo

Roth

et al. 2020

Fluids Barriers CNS

View full text Add to dashboard Cite

Background: Cerebrospinal fluid (CSF) is mainly produced by the choroid plexus (CP) located in brain ventricles. Although derived from blood plasma, it is nearly protein-free (~ 250-fold less) and contains about 2-20-fold less free amino acids, with the exception of glutamine (Gln) which is nearly equal. The aim of this study was to determine which amino acid transporters are expressed in mouse CP epithelium in order to gain understanding about how this barrier maintains the observed amino acid concentration gradient.Methods: Expression of amino acid transporters was assessed in isolated choroid plexuses (CPs) by qRT-PCR followed by localization studies using immunofluorescence with specific antibodies. The impact of LAT2 (Slc7a8) antiporter deletion on CSF amino acids was determined. Results:The purity of isolated choroid plexuses was tested on the mRNA level using specific markers, in particular transthyretin (Ttr) that was enriched 330-fold in CP compared to cerebral tissue. In a first experimental round, 14 out of 32 Slc amino acid transporters tested on the mRNA level by qPCR were selected for further investigation. Out of these, five were considered highly expressed, SNAT1 (Slc38a1), SNAT3 (Slc38a3), LAT2 (Slc7a8), ASC1 (Slc7a10) and SIT1 (Slc6a20b). Three of them were visualized by immunofluorescence: SNAT1 (Slc38a1), a neutral amino acid-Na + symporter, found at the blood side basolateral membrane of CP epithelium, while SNAT3 (Slc38a3), an amino acid-Na + symporter and H + antiporter, as well as LAT2 (Slc7a8), a neutral amino acid antiporter, were localized at the CSF-facing luminal membrane. In a LAT2 knock-out mouse model, CSF Gln was unchanged, whereas other amino acids normally 2-20-fold lower than in plasma, were increased, in particular the LAT2 uptake substrates leucine (Leu), valine (Val) and tryptophan (Trp) and some other amino acids such as glutamate (Glu), glycine (Gly) and proline (Pro). Conclusion:These results suggest that Gln is actively transported by SNAT1 from the blood into CP epithelial cells and then released luminally into CSF via SNAT3 and LAT2. Its efflux via LAT2 may drive the reuptake from the CSF of essential amino acid substrates of this antiporter and thereby participates to maintaining the amino acid gradient between plasma and CSF.

show abstract

“…Studies in postmortem tissue found unaltered d -serine levels in different brain regions in AD, including the frontal, temporal, and parietal cortices ( 114 – 116 ). On the other hand, three different studies observed an increase in d -serine levels in the CSF of patients with AD, but the size of the differences between AD and controls varied greatly between studies ( 113 , 117 , 118 ).…”

Section: Alzheimer’s Disease (Ad)mentioning

confidence: 99%

Potential and Challenges for the Clinical Use of d-Serine As a Cognitive Enhancer

Guercio

Panizzutti

2018

Front. Psychiatry

View full text Add to dashboard Cite

After 25 years of its discovery in the rat brain, d-serine is a recognized modulator of synaptic plasticity and cognitive processes through its actions on the NMDA-glutamate receptor. Importantly, cognitive impairment is a core feature of conditions, such as schizophrenia, Alzheimer's disease, depression, and aging, and is associated to disturbances in NMDA-glutamate receptors. The d-serine pathway has been associated with cognitive deficits and these conditions, and, for this reason, d-serine signaling is subject of intense research to probe its role in aiding diagnosis and therapy. Nevertheless, this has not resulted in new therapies being incorporated into clinical practice. Therefore, in this review we will address many questions that need to be solved by future studies, regarding d-serine pharmacokinetics, possible side effects, other strategies to modulate its levels, and combination with other therapies to increase its efficacy.

show abstract

CSF d-serine concentrations are similar in Alzheimer's disease, other dementias, and elderly controls

Cited by 44 publications

References 9 publications

Comparative analysis of cerebrospinal fluid metabolites in Alzheimer’s disease and idiopathic normal pressure hydrocephalus in a Japanese cohort

Comparative analysis of cerebrospinal fluid metabolites in Alzheimer’s disease and idiopathic normal pressure hydrocephalus in a Japanese cohort

Choroid plexus LAT2 and SNAT3 as partners in CSF amino acid homeostasis maintenance

Potential and Challenges for the Clinical Use of d-Serine As a Cognitive Enhancer

Contact Info

Product

Resources

About