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Relationship between apolipoprotein E4 genotype and white matter integrity in HIV-positive young adults in South Africa

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Abstract

HIV-associated dementia (HAD) is a serious neuropsychiatric disorder affecting people with AIDS. Host genotype may affect the pathogenesis of HIV in the central nervous system (CNS). One gene relevant to the individual variation in acquiring HAD may be Apolipoprotein E (ApoE). We aimed to investigate the relationship of ApoE genotype to neuropsychological function and white matter integrity of the corpus callosum in a region of interest a priori analysis of HIV-positive subjects with clade C HIV. Forty-five subjects underwent ApoE genotyping, neuropsychological testing, and diffusion tensor imaging (DTI). Subjects (n = 24) with at least one ε4 allele when compared to subjects with no ε4 allele (n = 19) had significantly decreased immediate and delayed recall on the Hopkins Verbal Learning test (p = 0.05) and significantly decreased fractional anisotrophy in the corpus callosum (p = 0.007). These data indicate that the ε4 allelic variant of ApoE is associated with memory impairment and white matter damage of the corpus callosum in HIV-positive subjects.

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References

  1. McArthur JC, Hoover DR, Bacellar H, Miller EN, Cohen BA, Becker JT, Graham NM, McArthur JH, Selnes OA, Jacobson LP et al (1993) Dementia in AIDS patients: incidence and risk factors. Multicenter AIDS Cohort Study. Neurology 43(11):2245–2252

    Article  PubMed  CAS  Google Scholar 

  2. Pemberton LA, Stone E, Price P, Van BF, Brew BJ (2008) The relationship between ApoE, TNFA, IL1a, IL1b and IL12b genes and HIV-1-associated dementia. HIV Med 9(8):677–680

    Article  PubMed  CAS  Google Scholar 

  3. Mahley RW, Ji ZS (1999) Remnant lipoprotein metabolism: key pathways involving cell-surface heparan sulfate proteoglycans and apolipoprotein E. J Lipid Res 40(1):1–16

    PubMed  CAS  Google Scholar 

  4. Smith JD (2000) Apolipoprotein E4: an allele associated with many diseases. Ann Med 32(2):118–127

    Article  PubMed  CAS  Google Scholar 

  5. Corder EH, Robertson K, Lannfelt L, Bogdanovic N, Eggertsen G, Wilkins J, Hall C (1998) HIV-infected subjects with the E4 allele for APOE have excess dementia and peripheral neuropathy. Nat Med 4(10):1182–1184

    Article  PubMed  CAS  Google Scholar 

  6. Nicoll JA, Roberts GW, Graham DI (1995) Apolipoprotein E epsilon 4 allele is associated with deposition of amyloid beta-protein following head injury. Nat Med 1(2):135–137

    Article  PubMed  CAS  Google Scholar 

  7. Valcour V, Shikuma C, Shiramizu B, Watters M, Poff P, Selnes OA, Grove J, Liu Y, Abdul-Majid KB, Gartner S et al (2004) Age, apolipoprotein E4, and the risk of HIV dementia: the Hawaii Aging with HIV Cohort. J Neuroimmunol 157(1–2):197–202

    Article  PubMed  CAS  Google Scholar 

  8. Esiri MM, Biddolph SC, Morris CS (1998) Prevalence of Alzheimer plaques in AIDS. J Neurol Neurosurg Psychiatry 65(1):29–33

    Article  PubMed  CAS  Google Scholar 

  9. Pemberton LA, Stone E, Price P, Van BF, Brew BJ (2008) The relationship between ApoE, TNFA, IL1a, IL1b and IL12b genes and HIV-1-associated dementia. HIV Med 9(8):677–680

    Google Scholar 

  10. Burt TD, Agan BK, Marconi VC, He W, Kulkarni H, Mold JE, Cavrois M, Huang Y, Mahley RW, Dolan MJ et al (2008) Apolipoprotein (apo) E4 enhances HIV-1 cell entry in vitro, and the APOE epsilon4/epsilon4 genotype accelerates HIV disease progression. Proc Natl Acad Sci USA 105(25):8718–8723

    Article  PubMed  CAS  Google Scholar 

  11. Twamley EW, Ropacki SA, Bondi MW (2006) Neuropsychological and neuroimaging changes in preclinical Alzheimer’s disease. J Int Neuropsychol Soc 12(5):707–735

    Article  PubMed  Google Scholar 

  12. Basser PJ (1995) Inferring microstructural features and the physiological state of tissues from diffusion-weighted images. NMR Biomed 8(7–8):333–344

    Article  PubMed  CAS  Google Scholar 

  13. Wu Y, Storey P, Cohen BA, Epstein LG, Edelman RR, Ragin AB (2006) Diffusion alterations in corpus callosum of patients with HIV. AJNR Am J Neuroradiol 27(3):656–660

    PubMed  CAS  Google Scholar 

  14. Chang L, Wong V, Nakama H, Watters M, Ramones D, Miller EN, Cloak C, Ernst T (2008) Greater than age-related changes in brain diffusion of HIV patients after 1 year. J. Neuroimmune. Pharmacol. 3(4):265–274

    Article  PubMed  Google Scholar 

  15. Thurnher MM, Castillo M, Stadler A, Rieger A, Schmid B, Sundgren PC (2005) Diffusion-tensor MR imaging of the brain in human immunodeficiency virus-positive patients. AJNR Am J Neuroradiol 26(9):2275–2281

    PubMed  Google Scholar 

  16. Salat DH, Tuch DS, Greve DN, van der Kouwe AJ, Hevelone ND, Zaleta AK, Rosen BR, Fischl B, Corkin S, Rosas HD et al (2005) Age-related alterations in white matter microstructure measured by diffusion tensor imaging. Neurobiol Aging 26(8):1215–1227

    Article  PubMed  CAS  Google Scholar 

  17. Taoka T, Iwasaki S, Sakamoto M, Nakagawa H, Fukusumi A, Myochin K, Hirohashi S, Hoshida T, Kichikawa K (2006) Diffusion anisotropy and diffusivity of white matter tracts within the temporal stem in Alzheimer disease: evaluation of the “tract of interest” by diffusion tensor tractography. AJNR Am J Neuroradiol 27(5):1040–1045

    PubMed  CAS  Google Scholar 

  18. Persson J, Lind J, Larsson A, Ingvar M, Cruts M, Van BC, Adolfsson R, Nilsson LG, Nyberg L (2006) Altered brain white matter integrity in healthy carriers of the APOE epsilon4 allele: a risk for AD? Neurology 66(7):1029–1033

    Article  PubMed  CAS  Google Scholar 

  19. de Leeuw FE, Richard F, de Groot JC, van Duijn CM, Hofman A, Van GJ, Breteler MM (2004) Interaction between hypertension, apoE, and cerebral white matter lesions. Stroke 35(5):1057–1060

    Article  PubMed  Google Scholar 

  20. Hixson JE, Vernier DT (1990) Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 31(3):545–548

    PubMed  CAS  Google Scholar 

  21. Joska JA, Westgarth-Taylor J, Myer L, Hoare J, Thomas KG, Combrinck M, Paul RH, Stein DJ, Flisher AJ (2011) Characterization of HIV-associated neurocognitive disorders among individuals starting antiretroviral therapy in South Africa. AIDS Behav 15(6):1197–1203

    Article  PubMed  Google Scholar 

  22. Hoare J, Fouche JP, Spottiswoode B, Joska JA, Schoeman R, Stein DJ, Carey PD (2010) White matter correlates of apathy in HIV-positive subjects: a diffusion tensor imaging study. J Neuropsychiatry Clin Neurosci 22(3):313–320

    Article  PubMed  Google Scholar 

  23. Hoare J, Fouche JP, Spottiswoode B, Sorsdahl K, Combrinck M, Stein DJ, Paul RH, Joska JA (2011) White-matter damage in clade C HIV-positive subjects: a diffusion tensor imaging study. J Neuropsychiatry Clin Neurosci 23(3):308–315

    Article  PubMed  Google Scholar 

  24. Forman SD, Cohen JD, Fitzgerald M, Eddy WF, Mintun MA, Noll DC (1995) Improved assessment of significant activation in functional magnetic resonance imaging (fMRI): use of a cluster-size threshold. Magn Reson Med 33(5):636–647

    Article  PubMed  CAS  Google Scholar 

  25. Joska JA, Combrinck M, Valcour VG, Hoare J, Leisegang F, Mahne AC, Myer L, Stein DJ (2010) Association between apolipoprotein E4 genotype and human immunodeficiency virus-associated dementia in younger adults starting antiretroviral therapy in South Africa. J Neurovirol 16(5):377–383

    Article  PubMed  CAS  Google Scholar 

  26. Carey CL, Woods SP, Rippeth JD, Gonzalez R, Moore DJ, Marcotte TD, Grant I, Heaton RK (2004) Initial validation of a screening battery for the detection of HIV-associated cognitive impairment. Clin Neuropsychol 18(2):234–248

    Article  PubMed  Google Scholar 

  27. Gray F, Scaravilli F, Everall I, Chretien F, An S, Boche D, dle-Biassette H, Wingertsmann L, Durigon M, Hurtrel B et al (1996) Neuropathology of early HIV-1 infection. Brain Pathol 6(1):1–15

    Article  PubMed  CAS  Google Scholar 

  28. Gongvatana A, Schweinsburg BC, Taylor MJ, Theilmann RJ, Letendre SL, Alhassoon OM, Jacobus J, Woods SP, Jernigan TL, Ellis RJ et al (2009) White matter tract injury and cognitive impairment in human immunodeficiency virus-infected individuals. J Neurovirol 15(2):187–195

    Article  PubMed  Google Scholar 

  29. Pocernich CB, Sultana R, Hone E, Turchan J, Martins RN, Calabrese V, Nath A, Butterfield DA (2004) Effects of apolipoprotein E on the human immunodeficiency virus protein Tat in neuronal cultures and synaptosomes. J Neurosci Res 77(4):532–539

    Article  PubMed  CAS  Google Scholar 

  30. Di PM, Di IF, Cherubini A, Blundo C, Casini AR, Sancesario G, Passafiume D, Caltagirone C, Spalletta G (2010) When, where, and how the corpus callosum changes in MCI and AD: a multimodal MRI study. Neurology 74(14):1136–1142

    Article  Google Scholar 

  31. Hallam BJ, Brown WS, Ross C, Buckwalter JG, Bigler ED, Tschanz JT, Norton MC, Welsh-Bohmer KA, Breitner JC (2008) Regional atrophy of the corpus callosum in dementia. J Int Neuropsychol Soc 14(3):414–423

    Article  PubMed  Google Scholar 

  32. Persson J, Nyberg L, Lind J, Larsson A, Nilsson LG, Ingvar M, Buckner RL (2006) Structure-function correlates of cognitive decline in aging. Cereb Cortex 16(7):907–915

    Article  PubMed  Google Scholar 

  33. Gold BT, Powell DK, Andersen AH, Smith CD (2010) Alterations in multiple measures of white matter integrity in normal women at high risk for Alzheimer’s disease. Neuroimage 52(4):1487–1494

    Article  PubMed  Google Scholar 

  34. Filippini N, Zarei M, Beckmann CF, Galluzzi S, Borsci G, Testa C, Bonetti M, Beltramello A, Ghidoni R, Benussi L et al (2009) Regional atrophy of transcallosal prefrontal connections in cognitively normal APOE epsilon4 carriers. J Magn Reson Imaging 29(5):1021–1026

    Article  PubMed  Google Scholar 

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Acknowledgments

JH has received support from the Biological Psychiatry special interest group of the South Africa Society of Psychiatrists and the Discovery Foundation Academic Award of South Africa. JJ has received support from the National Research Foundation, the Biological Psychiatry special interest group of the South Africa Society of Psychiatrists, the Medical Research Foundation of South Africa and the Faculty of Health Sciences Research Committee, University of Cape Town. DS is supported by the NRF and MRC.

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None to declare.

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Authors and Affiliations

  1. MRC Research Unit on Anxiety Disorders, Department of Psychiatry, Stellenbosch University, Stellenbosch, South Africa

    Jean-Paul Fouche

  2. Department of Psychiatry and Mental Health, University of Cape Town, Anzio Road Observatory, Cape Town, 7925, South Africa

    Jacqueline Hoare, Jenny Westgarth-Taylor, Dan J. Stein & John A. Joska

  3. Department of Neurology, University of Cape Town, Cape Town, South Africa

    Marc Combrinck

  4. MRC/UCT Medical Imaging Research Unit, Department of Human Biology, University of Cape Town, Cape Town, South Africa

    Bruce Spottiswoode

  5. Department of Radiological Sciences and Oncology, Stellenbosch University, Stellenbosch, South Africa

    Bruce Spottiswoode

Authors
  1. Jacqueline Hoare
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  2. Jenny Westgarth-Taylor
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  3. Jean-Paul Fouche
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  4. Marc Combrinck
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  7. John A. Joska
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Correspondence to Jacqueline Hoare.

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Hoare, J., Westgarth-Taylor, J., Fouche, JP. et al. Relationship between apolipoprotein E4 genotype and white matter integrity in HIV-positive young adults in South Africa. Eur Arch Psychiatry Clin Neurosci 263, 189–195 (2013). https://doi.org/10.1007/s00406-012-0341-8

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  • DOI: https://doi.org/10.1007/s00406-012-0341-8

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