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APOE ε4 allele and CSF APOE on Cognition in HIV-Infected Subjects

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Abstract

The significance of the cerebrospinal fluid (CSF) Apolipoprotein E (APOE) level and whether it might have differential effects on brain function due to the presence of APOE ε4 allele(s) in HIV-infected patients are unknown. However, APOE ε4 allele has been associated with greater incidence of HIV-associated dementia and accelerated progression of HIV infection. Here, we show further evidence for the role of APOE ε4 in promoting cognitive impairment. We measured the APOE levels in the CSF of HIV-infected individuals. HIV+ subjects showed lower CSF APOE proteins than SN controls (−19%, p = 0.03). While SN subjects with or without ε4 allele showed no difference in CSF APOE levels, ε4+ HIV+ subjects had similar levels to the SN subjects but higher levels than ε4− HIV+ subjects (+34%, p = 0.01). Furthermore, while HIV+ subjects with ε2 or ε3 allele(s) showed a positive relationship between their CSF APOE levels and cognitive performance on the speed of processing domain (r = +0.35, p = 0.05), ε4+ HIV+ subjects, in contrast, exhibited a negative relationship such that those with higher levels of CSF APOE(4) performed worse on the HIV Dementia Scale (r = −0.61, p = 0.02), had lower Global Cognitive Scores (r = −0.57, p = 0.03), and had poorer performance on tests involving learning (ε4 allele x [APOE] interaction, p = 0.01). Our findings also suggest that the relatively higher levels of CSF APOE in ε4+ HIV+ (having primarily APOE4 isoforms) may negatively impact the brain and lead to poorer cognitive outcomes, while those individuals without the ε4 allele (with primarily APOE2 or APOE3 isoforms) may show compensatory responses that lead to better cognitive performance.

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Acknowledgments

We thank our research participants and our community physicians (Dr. Drew Kovach, Dr. Cyril Goshima, Dr. Jennifer Frank, Dr. Arthur Johnson, Dr. Alan Tice, and others) who referred many of these participants to our research. We also thank Dr. Helenna Nakama, Dr. Michael Watters, Dr. Mary Ricardo-Dukelow, and our research coordinators for their participation in data collection.

None of the authors has conflicts of interest regarding the work presented.

This work was supported by research grants (2R01MH61427, 5R25MH080661, 2K24DA016170 and 1U54-NS056883) from the National Institutes of Health.

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Authors and Affiliations

  1. Pacific Biosciences Research Center, University of Hawaii, 1993 East-West Road, Honolulu, HI, 96822, USA

    Marilou A. Andres

  2. John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, 96813, USA

    Ute Feger, Sody Munsaka, Caroline S. Jiang & Linda Chang

  3. Department of Neurology, Johns Hopkins University, Baltimore, MD, 21287, USA

    Avindra Nath

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  1. Marilou A. Andres
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  2. Ute Feger
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Correspondence to Marilou A. Andres.

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Guarantors of the work: Marilou A. Andres, Ph.D. and Linda Chang, M.D.

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Andres, M.A., Feger, U., Nath, A. et al. APOE ε4 allele and CSF APOE on Cognition in HIV-Infected Subjects. J Neuroimmune Pharmacol 6, 389–398 (2011). https://doi.org/10.1007/s11481-010-9254-3

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