Event Abstract

The effect of apolipoprotein E (apoE) genotype on synchronous neural interactions (SNI) in healthy brains

  • 1 University of Minnesota, United States

In this study, we analyzed the effect of apolipoprotein E (apoE) genotype on SNI distributions in cognitively healthy subjects of various ages to determine the relations between apoE genotype and neural communication. ApoE is involved in lipid metabolism in the brain but its effects on brain function are not understood. Three apoE isoforms (E4, E3, and E2) are the result of cysteine-arginine interchanges at two sites: there are zero interchanges in E4, one interchange in E3, and two interchanges in E2. The resulting six apoE genotypes yield five groups with respect to the number of cysteine residues per mole (0-4 CysR/mole). The use of the number of CysR/mole to characterize the apoE molecule converts the categorical apoE genotype scale, consisting of 6 distinct genotypes above, to a 5-point continuous scale, allowing the use of statistical analyses suitable for continuous variables. Using such analyses, here we show for the first time that apoE affects in a graded and orderly manner neural communication, as assessed by analyzing the relation between the number of CysR/mole and synchronous neural interactions (SNI) measured by magnetoencephalography (MEG) in 130 cognitively healthy subjects. By investigating the statistical properties along the range of CysR/mole SNI distributions, the 4-CysR/mole (E2/2) SNI distribution was found to have unique properties. The special status of the 4-CysR/mole distribution was reinforced by the results of a hierarchical tree analysis (see figure 1) where the 4-CysR/mole (E2/2) SNI distribution occupied a separate division by itself and the remaining CysR/mole SNI distributions were placed at increasing distances from the 4-CysR/mole distribution, according to their number of CysR/mole, with the 0-CysR/mole (E4/4) being farthest away. These results support the idea that the number of CysR/mole is an important quantitative factor underlying the effect of apoE on SNI. In addition, these findings suggest that the 4-CysR/mole (E2/2) SNI distribution could serve as a reference distribution. When the SNI distributions of individual subjects were expressed as distances from this reference distribution, there was a substantial overlap among subjects of various CysR/mole. This orderly variation of SNI with the number of CysR/mole is in keeping with recent advances and ideas regarding the molecular mechanisms underlying the differential effects of apoE in the brain which emphasize (a) the healthier stability conferred on the apoE molecule by the increasing number of cysteine-arginine interchanges, with 4-CysR/mole (E2/2) being the best case, as opposed to (b) the instability and increased chance of toxic fragmentation of the apoE molecule with lower number of CysR/mole, with 0-CysR/mole (E4/4) as the worst case. Overall, we show for the first time that the apoE genotype affected the SNI distribution in a systematic and graded fashion, according to the number of CysR/mole in the apoE molecule.

Figure 1

Acknowledgements

This work was supported by the Minnesota Women Healthy Brain Aging Group. This material is based upon work partially supported by the National Science Foundation under Grant No. 00006595. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.

References

A. C. Leuthold, M. Y. Mahan, J. J. Stanwyck, A. Georgopoulos, and A. P. Georgopoulos, “The number of cysteine residues per mole in apolipoprotein E affects systematically synchronous neural interactions in women’s healthy brains.,” Experimental brain research, 2013, DOI: 10.1007/s00221-013-3464-x.

Keywords: Apolipoproteins E, Magnetoencephalography, synchronous neural interactions, Healthy Brains, Cysteine residues per mole

Conference: Neuroinformatics 2013, Stockholm, Sweden, 27 Aug - 29 Aug, 2013.

Presentation Type: Poster

Topic: Genomics and genetics

Citation: Mahan MY, Leuthold AC, Stanwyck JJ, Georgopoulos A and Georgopoulos AP (2013). The effect of apolipoprotein E (apoE) genotype on synchronous neural interactions (SNI) in healthy brains. Front. Neuroinform. Conference Abstract: Neuroinformatics 2013. doi: 10.3389/conf.fninf.2013.09.00064

Received: 09 Apr 2013; Published Online: 11 Jul 2013.

* Correspondence: Dr. Apostolos P Georgopoulos, University of Minnesota, Minneapolis, MN, 55455, United States, omega@umn.edu

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