Fatty Acids In Cerebrospinal Fluid Research Articles

Detection of Characteristic Phosphatidylcholine Containing Very Long Chain Fatty Acids in Cerebrospinal Fluid from Patients with X-Linked Adrenoleukodystrophy.

X-linked Adrenoleukodystrophy (X-ALD) is a rare genetic neurological disorder caused by a mutation of the ABCD1 gene that encodes a peroxisomal ABC protein ABCD1. ABCD1 has a role in transporting very long chain fatty acid (VLCFA)-CoA into the peroxisome for β-oxidation. ABCD1 dysfunction leads to reduced VLCFA β-oxidation and in turn increased VLCFA levels in the plasma and the cells of all tissues; these increased plasma levels have been used to diagnose X-ALD. It has been reported that plasma VLCFA is not correlated with the severity and disease phenotype of X-ALD. Therefore, we cannot predict the disease progression by the plasma VLCFA level. Cerebrospinal fluid (CSF) is constantly produced by brain, and thus levels of lipids containing VLCFA in CSF might be informative in terms of assessing X-ALD pathology. LC-MS/MS-based analysis showed that phosphatidylcholine (PC) containing VLCFA signals, such as PC 40 : 0(24 : 0/16 : 0), PC 42 : 0(26 : 0/16 : 0), PC 44 : 4(24 : 0/20 : 4) and PC 46 : 4(26 : 0/20 : 4) were characteristically detected only in the CSF from patients with X- ALD. In the present study, we analyzed limited number of patient's CSF samples (2 patients with X-ALD) due to the limitations of the availability for CSF samples from this rare disease. However, our finding would offer helpful information for studying the disease progression biomarkers in X-ALD. To our knowledge, this is the first report of analyzing lipids containing VLCFA in CSF from patients with X-ALD.

High-dose triglyceride DHA supplementation increases plasma and cerebrospinal fluid phospholipid DHA species.

It is not clear whether triglyceride DHA-based formulations (TG-DHA) can sufficiently enrich brain DHA. Animal studies suggest that phosphatidylcholine (PC) and lyso-phosphatidylcholine (LPC) lipids might be preferred brain DHA substrates. The goal of this study is to assess the effect of high-dose TG-DHA supplementation on DHA-containing PC (PC-DHA) and LPC (LPC-DHA) lipid species in plasma and total cerebrospinal fluid (CSF) DHA as a surrogate for brain DHA incorporation. We conducted a randomized clinical trial stratified by DHA treatment (n=14) and placebo (n=14) status in non-demented older participants (CDR ≤ 0.5, age ³ 55 years old). Participants were provided 2,040 mg DHA daily in the form of TG-DHA for six months. Plasma and CSF were obtained at baseline and after supplementation. Participants were also stratified by ApoE ε4 status, an allele known to increase Alzheimer's disease (AD) risk. PC and LPC lipid species from plasma and CSF were isolated and examined by LC/MS-MS. Total fatty acids in CSF were measured via GC/MS-MS. Among all participants, PC-DHA represented 39% of total DHA in plasma, while LPC-DHA represented 1.8% of total DHA. PC-DHA increased by 69% and 19% in plasma and CSF, respectively, following supplementation compared to placebo (p<0.0001 for both). Plasma LPC-DHA increased by 140% in the treatment group compared to placebo (p<0.0001). Increases in plasma PC-DHA and LPC-DHA were both significantly correlated to changes in total DHA in CSF (R=0.8 and 0.57, respectively, p<0.003 for both). A trend toward greater increases in PC-DHA in non-ApoE ε4 carriers compared to carriers were also observed. Our data indicate that high-dose TG-DHA supplementation effectively increases DHA phospholipid incorporation in plasma and CSF. We acknowledge that CSF may not exactly reflect brain lipid uptake but provides useful information on brain DHA bioavailability. Our findings support that high-dose TG DHA supplementation are brain penetrant and can help answer whether enriching brain DHA can slow down cognitive decline in patients at risk of AD.

Fatty acids and selected endocannabinoids content in cerebrospinal fluids from patients with neuroinfections

Neuroinfections are a significant medical problem and can have serious health consequences for patients. Their outcome, if not fatal, can be associated with permanent residual deficits. Cerebrospinal fluid (CSF) examination is commonly used for meningitis confirmation. Fatty acids (FA) are precursors of lipid mediators with pharmacological activity. They actively modulate inflammation as well as contribute to its resolution. Therefore the aim of this study was to determine the FA and selected endocannabinoids (ECB) content in the CSF obtained from patients with bacterial (BM) and viral meningitis (VM) using chromatographic techniques. A significantly lower level of saturated FA was found in patients with BM and VM as compared to controls. There was a significantly higher concentration of long-chain monounsaturated FA and polyunsaturated n-6 FA in the CSF obtained from patients with neuroinfection. Moreover, a significant reduction of n-3 FA in CSF obtained from patients with BM and VM was demonstrated. The highest amount of ECB was detected in the CSF of patients with VM: eicosapentaenoyl ethanolamide (1.65 pg/mL), docosahexaenoyl ethanolamide (655.5 pg/mL) and nervonoyl ethanolamide (3.09 ng/mL). Results indicate the participation of long-chain monounsaturated and polyunsaturated FA and their derivatives in the inflammatory process and likely in the process of resolution of inflammation during neuroinfection. It seems that the determination of the FA and ECB profile in CSF may be a valuable biomarker of health and may allow the development of new pharmacological strategies, therapeutic goals and fatty acids supplementation necessary in the fight against inflammation of the central nervous system.

Identifying Alzheimer's Disease Biomarkers by Analyzing Fatty Acids in Cerebrospinal Fluid and Urine

Although fatty acid oxidation is associated with Alzheimer's disease (AD) pathology, no links have been established between brain lipids and excreted oxidized products. We hypothesize that oxidation of brain polyunsaturated fatty acids (PUFA) can generate dicarboxylic acids (DCA) excreted in urine by AD subjects at different rates compared with cognitively healthy (CH) subjects. Furthermore, this trend can be extended to differentiate CH subjects with normal cerebrospinal fluid (CSF) Aβ42/tau ratios (CH‐NAT) and CH subjects with pathological CSF Aβ42/tau ratios (CH‐PAT).Subjects &gt; 70 years were classified as CH (n=64) or AD (n=26) after neuropsychological assessment. CSF Aβ42 and Tau levels were determined using an ELISA‐based method and a logistic regression of Aβ42/tau ratios used to classify CH‐NAT and CH‐PAT. CSF was fractionated and PUFA levels quantified in supernatant fluid (SF), nanoparticles (NP), and unesterified fatty acid (UFA). DCA was derivatized to pentafluorobenzyl ester, and quantified using gas chromatography and isotope dilution negative ion chemical ionization mass spectrometry. PUFA data is expressed as a percentage of fatty acids detected in CSF fractions while DCA is calculated as a percentage of 7 DCAs (C4–C10) in urine. Links between urinary DCAs and CSF PUFAs were determined using Spearman's ranked correlation.C10 DCA negatively correlated with 6 of 8 PUFAs in SF from CH and also negatively correlated with C20:3n‐3 and C22:6n‐3 in SF from CH‐NAT. In contrast, C9 DCA negatively correlated with 7 of 8 PUFAs in SF from AD. C6 and C8 DCAs positively correlated with SF C18:3n‐3 and C20:3n‐3 in AD, respectively, while C6 DCA negatively correlated with SF C18:2n‐6 from CH‐NAT. C4 DCA negatively correlated with C18:2n‐6, C20:4n‐6, and C22:6n‐3 in SF from CH‐PAT, while C7 DCA positively correlated with C20:4n‐6 in SF from CH‐PAT. In the NP fraction of CH, C4 DCA positively correlated with C20:2n‐6, C20:3n‐3, C20:5n‐3, and C22:5n‐3 PUFAs, while C8 DCA negatively correlated with C20:5n‐3. Only C9 DCA positively correlated with C20:4n‐6 in AD NP fractions. Interestingly, no correlations were found in the NP fraction from CH‐NAT. However, C8 DCA negatively correlated with NP C20:3n‐3, C20:5n‐3, and C22:5n‐3 and C4 DCA positively correlated with NP C20:5n‐3 from CH‐PAT. For UFA of CH, C6 DCA negatively correlated with C20:2n‐6, C20:3n‐3, and C22:6n‐3, while C5 and C7 DCAs positively correlated with homo‐γ‐C20:3n‐6 and C18:2n‐6, respectively. For UFA of CH‐NAT, C4 DCA positively correlated with homo‐γ‐C20:3n‐6, C5 and C8 DCAs negatively correlated with homo‐γ‐C20:3n‐6, and C7 DCA negatively correlated with C18:2n‐6. C5 DCA positively correlated with C18:2n‐6 in UFA from CH‐PAT. C8 DCA positively correlated with unesterified C22:6n‐3, while C9 DCA negatively correlated with unesterified C20:5n‐3 in AD subjects.Differential correlation of urinary DCAs with CSF PUFAs in clinical groups suggests a link with AD pathology. PUFAs and DCAs that segregate CH‐NAT from CH‐PAT are potential biomarkers of early AD.Support or Funding InformationL.K. Whittier and the Helen Posthuma FoundationsThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Differential fatty acid analysis of cerebrospinal fluid in infants and young children with suspected meningitis

Meningitis is relatively common in infants and young children and can cause permanent brain damage. The aim of this study was to determine whether meningitis is associated with fatty acids in cerebrospinal fluid (CSF). CSF samples from children between 3months and 6years of age admitted to the Tabriz public hospitals who met clinical criteria of meningitis were collected at enrollment. A total of 81 samples were analyzed for fatty acid profile by gas-liquid chromatography. Children with a purulent meningitis demonstrated a higher percentage of oleic acid (p<0.05, >10%) and lower percentages of omega-3 polyunsaturated fatty acids (p<0.001, <-40%) than aseptic meningitis and nonmeningitis groups did. There was an inverse relationship between CSF long-chain omega-3 fatty acids and the total number of leukocytes and differential counts of neutrophils and lymphocytes in the purulent meningitis group. Moreover, significantly lower omega-3 fatty acids (p=0.001, -37%) and higher ratio of n-6/n-3 (p=0.02, -29%) were found in patients with purulent meningitis with sepsis than in those with meningitis and no sepsis. This study provides evidence that purulent meningitis and its complication with sepsis are associated with important disturbances in CSF fatty acids, mainly deficiency in long-chain omega-3 polyunsaturated fatty acids.

Correlation of secretory phospholipase-A2 activity and fatty acids in cerebrospinal fluid with liver enzymes tests

Introduction: The aim was to determine whether secretory phospholipase-A2 (sPLA2) activity and fatty acids in cerebrospinal fluid (CSF) are correlated with liver enzymes tests. Methods: CSF and serum samples were collected from 49 patients (age 18-65) as part of routine diagnostic testing. Along with serum liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), the fatty acid composition of CSF was measured by gas liquid chromatography. CSF enzyme activities of sPLA2 were measured using the standard assay with diheptanoyl thio-phosphatidylcholin as substrate. Results: The saturated fatty acids (SFAs) including palmitic acid and stearic acid were positively, and the unsaturated fatty acids including oleic acid and linoleic acid were negatively correlated with liver enzymes tests. In regression analysis with adjustment for body mass index (BMI), the elevated liver enzymes tests were positively associated with activity of sPLA2 (β > 0.31, P 0.38, P < 0.010) and negatively with total monounsaturated fatty acids (MUFAs) (β < -0.40, P < 0.001) contents of CSF. Conclusion: CSF activity of sPLA2 and fatty acids may be linked to peripheral markers of liver function, suggesting an indirect impact of central fatty acids on hepatocytes function and metabolism.

Effects of a DHA rich n‐3 fatty acid supplementation on fatty acid composition in cerebrospinal fluid in Alzheimer disease. The OmegAD study

BackgroundLittle is known about the transfer of essential fatty acids (FA) across the human blood‐brain barrier (BBB) in adulthood.ObjectiveWill oral supplementation for 6 mo with omega‐3 fatty acids (n‐3 FA), high in DHA, change the FA profile in cerebrospinal fluid (CSF) in patients with Alzheimer's disease (AD)?MethodsFA in CSF were analyzed by gas chromatography and mass spectrometry in 33 patients; 18 received n‐3 FA and 15 placebo. Participants were part of the OmegAD Study, where 204 patients with mild AD received 2.3 g n‐3 FA daily or placebo for 6 mo in a randomized fashion. Correlation analyses were made with plasma FA, CSF markers of AD and of inflammation.ResultsAt 6 mo a significant increase in CSF (and plasma) EPA, DHA and total n‐3 levels were noted in the n‐3 FA group, whereas no changes were observed in the placebo group. Changes of CSF DHA levels correlated significantly to changes of total and phosphorylated Tau and soluble IL‐1RII in CSF, i.e. the more the FA increased, the more the AD biomarkers decreased.SummaryN‐3 FA supplementation conferred discrete changes of n‐3 FA in CSF, suggesting transfer over the adult BBB. Significant correlations between CSF n‐3 FA and CSF AD markers suggest possible relationships.

Associations of Fatty Acids in Cerebrospinal Fluid with Peripheral Glucose Concentrations and Energy Metabolism

Rodent experiments have emphasized a role of central fatty acid (FA) species, such as oleic acid, in regulating peripheral glucose and energy metabolism. Thus, we hypothesized that central FAs are related to peripheral glucose regulation and energy expenditure in humans. To test this we measured FA species profiles in cerebrospinal fluid (CSF) and plasma of 32 individuals who stayed in our clinical inpatient unit for 6 days. Body composition was measured by dual energy X-ray absorptiometry and glucose regulation by an oral glucose test (OGTT) followed by measurements of 24 hour (24EE) and sleep energy expenditure (SLEEP) as well as respiratory quotient (RQ) in a respiratory chamber. CSF was obtained via lumbar punctures; FA concentrations were measured by liquid chromatography/mass spectrometry. As expected, FA concentrations were higher in plasma compared to CSF. Individuals with high concentrations of CSF very-long-chain saturated FAs had lower rates of SLEEP. In the plasma moderate associations of these FAs with higher 24EE were observed. Moreover, CSF monounsaturated long-chain FA (palmitoleic and oleic acid) concentrations were associated with lower RQs and lower glucose area under the curve during the OGTT. Thus, FAs in the CSF strongly correlated with peripheral metabolic traits. These physiological parameters were most specific to long-chain monounsaturated (C16∶1, C18∶1) and very-long-chain saturated (C24∶0, C26∶0) FAs. Conclusions: Together with previous animal experiments these initial cross-sectional human data indicate that central FA species are linked to peripheral glucose and energy homeostasis.

Measurement of free fatty acids in cerebrospinal fluid from patients with hemorrhagic and ischemic stroke

Free fatty acid (FFA) concentrations in cerebrospinal fluid (CSF) from patients with ischemic and hemorrhagic stroke ( n=25) and in contemporary controls ( n=73) were examined using HPLC. Concentrations of CSF FFAs from ischemic and hemorrhagic stroke patients obtained within 48 h of the insult were significantly greater than in control patients. Higher concentrations of polyunsaturated fatty acids (PUFAs) in CSF obtained within 48 h of insult were associated with significantly lower ( P<0.05) admission Glasgow Coma Scale scores and worse outcome at the time of hospital discharge, using the Glasgow Outcome Scale ( P<0.01).

Reduced Levels of Cholesterol, Phospholipids, and Fatty Acids in Cerebrospinal Fluid of Alzheimer Disease Patients Are Not Related to Apolipoprotein E4

Apolipoprotein E4 (apoE4) has been identified as a major risk factor for Alzheimer disease (AD). Previously it has been reported that levels of apoE are reduced in cerebrospinal fluid (CSF) of AD patients. Because it is known that apoE4 affects plasma lipid metabolism, we examined whether the presence of apoE4 might correlate with an altered lipid metabolism in the CSF of control subjects and AD patients. ApoE and lipid concentrations were determined in postmortem ventricular CSF of 30 neuropathologically confirmed AD cases and 31 age-matched control patients. ApoE genotyping was performed on frozen brain tissue of the same patients. In line with other reports, we found an increased APOE*4 allele frequency in the AD group (0.461) when compared with the control group (0.225). ApoE levels in CSF of AD patients were not significantly reduced when compared with the controls (mean +/-SD: 63+/-55 and 82+/-62 microg/dL for AD and controls, respectively). However, in the CSF of AD patients levels of free and esterified cholesterol (0.13+/-0.09 and 0.25+/-0.19 mg/dL, and 0.25+/-0.19 and 0.42+/-0.34, respectively), phospholipids (0.2+/-0.1 and 3.5+/-5.0 mg/dL) and, suprisingly, also fatty acids (4.5+/-3.2 and 28.0+/-18.5 micromol/L) were found to be significantly reduced. After correction for age, sex, postmortem delay, and pH the levels of phospholipids, fatty acids, and free cholesterol were still significantly reduced (p = 0.021, p = 0.026, andp = 0.012, respectively). The apoE and lipid levels in CSF of AD-and control patients appeared not to be affected by the number of APOE*4 alleles. In conclusion, our results suggest an altered lipid homeostasis in the brain of AD patients that is not related to the presence of apoE4. It is, therefore, unlikely that an effect of apoE4 on brain lipid metabolism is the underlying mechanism behind the role of apoE4 in the development of AD.

Spectrum of total fatty acids in cerebrospinal fluid determined by gas chromatography

A simple gas—liquid chromatographic method for the determination of the spectrum of fatty acids in a small volume of cerebrospinal fluid (CSF) is presented. In a group of 49 neurological patients it has been found that in the CSF of the controls ( n = 12) there are the following main fatty acids: oleic (27.28%), palmitic (23.23%), stearic (12.21%), linoleic (7.66%), myristic (5.02%), and palmitoleic (4.51%). Altogether 28 fatty acid methyl esters (FAMEs) from 12:0 to 22:2 have been tentatively identified. The majority of them appeared irregularly, sometimes in less than in 10% of cases. The composition of FAMEs in the CSF of patients with lumbar discopathy and with acute ischaemic cerebrovascular accidents does not differ from the control group. A significant difference ( P<0.01) has been found in the group of hypophyseal adenomas in which the amounts of practically all saturated FAMEs with an odd carbon number are elevated. The same applies to the 18:0 and 20:0 compounds. In the group of atrophic and degenerative CNS processes the palmitic and stearic acids predominated to the detriment of oleic and linoleic acids.

DETERMINATION OF FATTY ACIDS IN CEREBROSPINAL FLUID. 3. QUANTITATIVE AND QUALITITATIVE STUDIES IN SOME NEUROLOGICAL AND PSYCHIATRIC DISORDERS.

DETERMINATION OF FATTY ACIDS IN CEREBROSPINAL FLUID. 3. QUANTITATIVE AND QUALITITATIVE STUDIES IN SOME NEUROLOGICAL AND PSYCHIATRIC DISORDERS.

Determination of Fatty Acids in Cerebrospinal Fluid II. Qualitative and Quantitative Studies by a Combination of Alkali Titration and Gas Chromatography

Determination of Fatty Acids in Cerebrospinal Fluid II. Qualitative and Quantitative Studies by a Combination of Alkali Titration and Gas Chromatography

Determination of Fatty Acids in Cerebrospinal Fluid II. Qualitative and Quantitative Studies by a Combination of Alkali Titration and Gas Chromatography

Determination of Fatty Acids in Cerebrospinal Fluid II. Qualitative and Quantitative Studies by a Combination of Alkali Titration and Gas Chromatography