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Blood amyloid-β protein isoforms are affected by HIV-1 in a subtype-dependent pattern

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Abstract

This study aimed to compare serum amyloid processing biomarkers among HIV subtype B (n = 25), HIV subtype C (n = 26), healthy HIV-negative controls (n = 18), and patients with Alzheimer’s disease (AD; n = 24). Immunoassays were used to measure main soluble Aβ isoforms Aβ38, Aβ40, Aβ42, and Aβ-total in serum and cerebrospinal fluid (CSF). People living with HIV (PLWH) and HIV(−) samples, including AD samples, were compared for gender and age, while HIV subtypes were compared for nadir CD4 and plasma viral load suppression. CSF/serum ratios of Aβ40, Aβ42, and Aβ-total were lower in HIV-1C group than in HIV-1B group (p = 0.020, 0.025, and 0.050, respectively). In serum, these biomarkers were comparable. Serum Aβ isoforms were significantly lower in PLWH than in AD. Serum Aβ42 levels in PLWH were decreased compared to those in control group, thus similar to Aβ42 alterations in CSF; these results were different from those observed in AD. Impaired cellular immunity, low CD4 cell count (nadir or current) influences serum Aβ metabolism in HIV-1B but not HIV-1C. However, in PLWH overall, but not in individual HIV subtype groups, greater CD4 recovery, calculated as the difference between current and nadir CD4, correlated with Aβ42/Aβ40 ratio in serum (rs 0.246; p = 0.0479). No significant correlation was found with global deficit score (GDS), an index of neurocognitive performance, age, or duration of infection. These findings are consistent with those of subtype-dependent amyloid processing in blood in chronic HIV disease.

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Acknowledgments

This work was supported by the following grants: National Institute of Health, NIH R21 MH76651 (Ellis, Ronald J; Almeida, Sergio M.), S10 RR31646 (Letendre, Scott), K24 MH097673(Letendre, Scott); University of California, San Diego, Center for AIDS Research (CFAR), an NIH-funded program (P30 AI036214), which is supported by the following NIH Institutes and Centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, and NIDDK. The HIV Neurobehavioral Research Center (HNRC) is supported by Center award P30MH062512 from NIMH. The San Diego HIV Neurobehavioral Research Center [HNRC] group is affiliated with the University of California, San Diego, the Naval Hospital, San Diego, and the Veterans Affairs San Diego Healthcare System, and includes: Director: Robert K. Heaton, Ph.D., Co-Director: Igor Grant, M.D.; Associate Directors: J. Hampton Atkinson, M.D., Ronald J. Ellis, M.D., Ph.D., and Scott Letendre, M.D.; Center Manager: Thomas D. Marcotte, Ph.D.; Jennifer Marquie-Beck, M.P.H.; Melanie Sherman; Neuromedical Component: Ronald J. Ellis, M.D., Ph.D. (P.I.), Scott Letendre, M.D., J. Allen McCutchan, M.D., Brookie Best, Pharm.D., Rachel Schrier, Ph.D., Debra Rosario, M.P.H.; Neurobehavioral Component: Robert K. Heaton, Ph.D. (P.I.), J. Hampton Atkinson, M.D., Steven Paul Woods, Psy.D., Thomas D. Marcotte, Ph.D., Mariana Cherner, Ph.D., David J. Moore, Ph.D., Matthew Dawson; Neuroimaging Component: Christine Fennema-Notestine, Ph.D. (P.I.), Monte S. Buchsbaum, M.D., John Hesselink, M.D., Sarah L. Archibald, M.A., Gregory Brown, Ph.D., Richard Buxton, Ph.D., Anders Dale, Ph.D., Thomas Liu, Ph.D.; Neurobiology Component: Eliezer Masliah, M.D. (P.I.), Cristian Achim, M.D., Ph.D.; Neurovirology Component: David M. Smith, M.D. (P.I.), Douglas Richman, M.D.; International Component: J. Allen McCutchan, M.D., (P.I.), Mariana Cherner, Ph.D.; Developmental Component: Cristian Achim, M.D., Ph.D.; (P.I.), Stuart Lipton, M.D., Ph.D.; Participant Accrual and Retention Unit: J. Hampton Atkinson, M.D. (P.I.), Jennifer Marquie-Beck, M.P.H.; Data Management and Information Systems Unit: Anthony C. Gamst, Ph.D. (P.I.), Clint Cushman; Statistics Unit: Ian Abramson, Ph.D. (P.I.), Florin Vaida, Ph.D. (Co-PI), Bin Tang, Ph.D., Anya Umlauf, M.S.

The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, nor the United States Government.

Study funding

This study was funded by CFAR (International Pilot Grant P30 AI036214 and CFAR Visiting Researcher Grant PTHMON7) and NIMH (R21 MH076651-01).

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Authors and Affiliations

  1. Hospital de Clínicas – UFPR, Seção de Virologia, Setor Análises Clínicas Rua Padre Camargo, Universidade Federal do Paraná, Curitiba, Paraná, 80060-240, Brazil

    Sérgio M. de Almeida, Clea E. Ribeiro, Indianara Rotta & Meiri Batistela

  2. University of California San Diego, San Diego, CA, USA

    Scott Letendre, Michael Potter, Bin Tang, Florin Vaida & Ronald J. Ellis

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  1. Sérgio M. de Almeida
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  2. Clea E. Ribeiro
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  3. Indianara Rotta
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Correspondence to Sérgio M. de Almeida.

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de Almeida, S.M., Ribeiro, C.E., Rotta, I. et al. Blood amyloid-β protein isoforms are affected by HIV-1 in a subtype-dependent pattern. J. Neurovirol. 26, 3–13 (2020). https://doi.org/10.1007/s13365-019-00783-6

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