Apolipoprotein E levels in cerebrospinal fluid and the effects of ABCAI polymorphisms

Department of Neurology, Washington University, St, Louis, MO, USA.
Molecular Neurodegeneration (Impact Factor: 6.56). 04/2007; 2(1):7. DOI: 10.1186/1750-1326-2-7
Source: PubMed


Animal studies suggest that brain apolipoprotein E (apoE) levels influence amyloid-β (Aβ) deposition and thus risk for Alzheimer's disease (AD). We have previously demonstrated that deletion of the ATP-binding cassette A1 transporter (ABCA1) in mice causes dramatic reductions in brain and cerebrospinal fluid (CSF) apoE levels and lipidation. To examine whether polymorphisms in ABCA1 affect CSF apoE levels in humans, we measured apoE in CSF taken from 168 subjects who were 43 to 91 years old and were either cognitively normal or who had mild AD. We then genotyped the subjects for ten previously identified ABCA1 single nucleotide polymorphisms (SNPs).
In all subjects, the mean CSF apoE level was 9.09 μg/ml with a standard deviation of 2.70 μg/ml. Levels of apoE in CSF samples taken from the same individual two weeks apart were strongly correlated (r2 = 0.93, p < 0.01). In contrast, CSF apoE levels in different individuals varied widely (coefficient of variation = 46%). CSF apoE levels did not vary according to AD status, APOE genotype, gender or race. Average apoE levels increased with age by ~0.5 μg/ml per 10 years (r2 = 0.05, p = 0.003). We found no significant associations between CSF apoE levels and the ten ABCA1 SNPs we genotyped. Moreover, in a separate sample of 1225 AD cases and 1431 controls, we found no association between the ABCA1 SNP rs2230806 and AD as has been previously reported.
We found that CSF apoE levels vary widely between individuals, but are stable within individuals over a two-week interval. AD status, APOE genotype, gender and race do not affect CSF apoE levels, but average CSF apoE levels increase with age. Given the lack of association between CSF apoE levels and genotypes for the ABCA1 SNPs we examined, either these SNPs do not affect ABCA1 function or if they do, they do not have strong effects in the CNS. Finally, we find no evidence for an association between the ABCA1 SNP rs2230806 and AD in a large sample set.

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Available from: Scott Smemo, Feb 12, 2014
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    • "For example, the apoE:Aβ ratios reported for human CSF are in the range of 1:0.006-0.02 [72-74]. In addition, density gradient centrifugation is known to induce loss of (apolipo)proteins from lipoproteins [67], which would likely effect the components of the apoE/Aβ complex isolated by this method. "
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    • "A total of 14 studies have been conducted to investigate the association of ABCA1 gene polymorphisms with the risk for AD (Wollmer et al., 2003; Katzov et al., 2004; Li et al., 2004; Kolsch et al., 2006; Shibata et al., 2006; Chu et al., 2007; Rodriguez-Rodriguez et al., 2007, 2009, 2010; Sundar et al., 2007; Wahrle et al., 2007; Wang and Jia, 2007; Wavrant-De Vrieze et al., 2007; Reynolds et al., 2009). Eight of these studies link single nucleotide polymorphisms (SNP) in the ABCA1 gene to an increased risk for AD (Katzov et al., 2004; Shibata et al., 2006; Chu et al., 2007; Rodriguez-Rodriguez et al., 2007; Sundar et al., 2007; Wang and Jia, 2007; Wavrant-De Vrieze et al., 2007; Reynolds et al., 2009). "
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