Neuronal fiber bundle lengths in healthy adult carriers of the ApoE4 allele: A quantitative tractography DTI study

Abstract

The epsilon 4 (e4) isoform of apolipoprotein E (ApoE) is a known genetic risk factor for suboptimal brain health. Morphometry studies of brains with Alzheimer’s disease have reported significant alterations in temporal lobe brain structure of e4 carriers, yet it remains unclear if the presence of an e4 allele is associated with alterations in the microstructure of white matter fiber bundles in healthy populations. The present study used quantitative tractography based on diffusion tensor imaging (qtDTI) to examine the influence of the e4 allele on temporal lobe fiber bundle lengths (FBLs) in 64 healthy older adults with at least one e4 allele (carriers, N = 23) versus no e4 allele (non-carriers, N = 41). Subtests from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were also analyzed to examine memory performance between groups. Analyses revealed shorter FBLs in the left uncinate fasciculus (UF) (p = .038) of e4 carriers compared to non-carriers. By contrast, neither FBLs specific to the temporal lobe nor memory performances differed significantly between groups. Increased age correlated significantly with shorter FBL in the temporal lobe and UF, and with decreased performance on tests of memory. This is the first study to utilize qtDTI to examine relationships between FBL and ApoE genotype. Results suggest that FBL in the UF is influenced by the presence of an ApoE e4 allele (ApoE4) in healthy older adults. Temporal lobe FBLs, however, are more vulnerable to aging than the presence of an e4 allele.

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Acknowledgments

Study Funding: Supported by NIH/NINDS grants R01 NS052470 and R01 NS039538, and NIH/NIMH grant R21 MH090494. DNA extractions were performed by Genetic Repositories Australia, an Enabling Facility, which is supported by an Australian National Health and Medical Research Council Grant (401184). Recruitment database searches were supported in part by NIH/NCRR grant UL1 TR000448.

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There are no actual or potential conflicts of interest for any of the authors on this manuscript.

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Correspondence to Lauren E. Salminen.

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Salminen, L.E., Schofield, P.R., Lane, E.M. et al. Neuronal fiber bundle lengths in healthy adult carriers of the ApoE4 allele: A quantitative tractography DTI study. Brain Imaging and Behavior 7, 274–281 (2013). https://doi.org/10.1007/s11682-013-9225-4

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Keywords

  • ApoE
  • ApoE4
  • Tractography
  • DTI
  • White matter
  • Fiber bundle lengths
  • Aging