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A High Throughput, Multiplexed and Targeted Proteomic CSF Assay to Quantify Neurodegenerative Biomarkers and Apolipoprotein E Isoforms Status
Published on: October 20, 2016
Effect of apolipoprotein E (apoE) phenotype on the apoE content of CSF-HDL in children
Satoshi Hirayama1, Takashi Miida, Konen Obayashi
1Division of Endocrinology and Metabolism, Department of Homeostatic Regulation and Developments, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi 1-757, Niigata City, Niigata 951-8510, Japan.
Insights
The apolipoprotein E (apoE) phenotype does not alter cerebrospinal fluid (CSF) high-density lipoprotein (HDL) composition in children. However, the CSF-apoE/phospholipid ratio is higher in children than adults, suggesting developmental differences.
Area of Science:
- Neuroscience
- Biochemistry
- Genetics
Background:
- Cerebrospinal fluid (CSF) high-density lipoprotein (HDL) is primarily composed of apolipoprotein E (apoE).
- Neuronal apoE receptors suggest CSF-apoE-HDL's role in central nervous system (CNS) development.
- The apoE phenotype influences adult Alzheimer's disease risk, prompting investigation in children.
Purpose of the Study:
- To investigate if the apolipoprotein E (apoE) phenotype affects the composition and concentration of CSF-HDL in children.
- To compare CSF-HDL parameters between children and adults based on apoE phenotype.
Main Methods:
- Determined apoE phenotype in 107 neurologically normal individuals (67 children) using isoelectric focusing.
- Measured CSF concentrations of apoE, total cholesterol (TC), and phospholipids (PL).
- Analyzed apoE/PL ratios in CSF samples.
Main Results:
- No significant differences in CSF-apoE, TC, or PL concentrations or apoE/PL ratio were found across apoE phenotypes in children.
- CSF-apoE/PL ratio was significantly higher in children compared to adults.
- Allele frequencies for apoE epsilon 4, 3, and 2 were 0.082, 0.888, and 0.030, respectively.
Conclusions:
- The apoE phenotype does not influence CSF-HDL composition or concentration in pediatric subjects.
- Speculation that CSF-HDL enriched with apoE may protect apoE4 carriers from impaired CNS development in childhood.
Background:
The majority of the lipoprotein in cerebrospinal fluid (CSF) is apolipoprotein E (apoE)-containing HDL. Since neuronal cells express lipoprotein receptors which recognize apoE, apoE in CSF-HDL is believed to be important for the development of central nervous system (CNS) in children. In adults, the apoE phenotype affects the plasma apoE concentration and the epsilon 4 allele is a risk factor for Alzheimer's disease. Due to the requirement for CNS development, we examined whether the apoE phenotype affects the composition and concentration of CSF-HDL in children.
Methods:
We determined the apoE phenotype in 107 neurologically normal subjects, including 67 children (<20 years), by isoelectronic focusing. We also measured apoE, total cholesterol (TC), and phospholipid (PL) concentrations in the CSF.
Results:
The respective frequencies of apoE4/3, E3/3 and E3/2 were 16.4%, 77.6%, and 6.0%. The allele frequencies of epsilon 4, epsilon 3, and epsilon 2 were 0.082, 0.888, and 0.030, respectively. There were no significant differences in the CSF-apoE, TC, or PL concentrations or the apoE/PL ratio among the apoE phenotypes. However, the CSF-apoE/PL ratio was significantly higher in children than in adults.
Conclusion:
The apoE phenotype does not affect the composition or concentration of CSF-HDL in children. We speculate that an apoE4 carrier is prevented in childhood from the impaired development of central nervous system by CSF-HDL enriched with apoE.
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