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Alzheimer’s disease neuropathology may not predict functional impairment in HIV: a report of two individuals

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Abstract

With aging of HIV populations, there is concern that Alzheimer’s disease (AD) may become prevalent and difficult to distinguish from HIV-associated neurocognitive disorders. To date, there are no reports documenting histologically verified Alzheimer’s neuropathology in individuals with HIV and dementia. Herein, we report two antiretroviral-treated, virally suppressed, HIV-infected individuals autopsied by the Manhattan HIV Brain Bank. Subject A presented to study at 52 years, already dependent in instrumental activities of daily living (ADLs), with severe cognitive impairment inclusive of learning and memory dysfunction. Her history was significant for educational disability and head trauma. She had rapid cognitive decline and, by death at age 59 years, was bed-bound, incontinent, and non-communicative. At autopsy, she exhibited severe AD neuropathologic change (NIA-AA score A3B3C3) and age-related tau astrogliopathy (ARTAG). She was homozygous for APOE ε3/ε3. No HIV DNA was detected in frontal lobe by nested polymerase chain reaction. Subject B was a community dwelling 81-year-old woman who experienced sudden death by pulmonary embolus. Prior to death, she was fully functional, living independently, and managing all ADLs. At autopsy, she displayed moderate amyloid and severe tau AD neuropathologic changes (A2B3C2), ARTAG, and cerebral congophilic angiopathy. She was an APOE ε3/ε4 heterozygote, and HIV DNA, but not RNA, was detected in frontal lobe, despite 20 years of therapy-induced viral suppression. We conclude that in the setting of HIV, AD neuropathology may occur with or without symptomatic cognitive dysfunction; as with seronegative individuals, there are likely to be complex factors in the generation of clinically relevant impairments.

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Acknowledgements

The authors thank the staff, patients, and families of the MHBB for their contributions. Tissues from the subjects described herein are available on request from the National NeuroAIDS Tissue Consortium.

Funding

This study is supported in part by NIH grants U24MH100931 (The Manhattan HIV Brain Bank; MHBB), K01DA035725 (Dopamine Neurobiology in HIV-associated cognitive dysfunction and substance use), R01NS095252 (Mechanisms of age-related tauopathy), RO1AG054008 (Regulation of tau expression in Alzheimer disease and aging), and UL1TR001433 (funding the Icahn School of Medicine Clinical Research Center).

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Authors and Affiliations

  1. Department of Neurology, The Icahn School of Medicine at Mount Sinai, Mount Sinai Medical Center, Gustave L Levy Place, Box 1137, New York, NY, 10029, USA

    Susan Morgello, Michelle Jacobs, Jacinta Murray, Desiree Byrd, Letty Mintz, Gregory Meloni & Christina Chon

  2. Department of Neuroscience and Pathology, The Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA

    Susan Morgello & John Crary

  3. Department of Psychiatry, The Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA

    Desiree Byrd

  4. Department of Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA

    Eric Neibart

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  1. Susan Morgello
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  2. Michelle Jacobs
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Correspondence to Susan Morgello.

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This study is monitored and approved by the institutional review board of the Icahn School of Medicine at Mount Sinai (ISMMS).

Conflict of interest

Susan Morgello, MD: Receives salary support from grants provided to the Icahn School of Medicine from the National Institutes of Health.

Michelle Jacobs, PhD: Receives salary support from grants provided to the Icahn School of Medicine from the National Institutes of Health.

Jacinta Murray, BS: Receives salary support from grants provided to the Icahn School of Medicine from the National Institutes of Health.

Desiree Byrd, PhD: Receives salary support from grants provided to the Icahn School of Medicine from the National Institutes of Health.

Eric Neibart, MD: Has no conflicts to report.

Letty Mintz, ANP: Receives salary support from grants provided to the Icahn School of Medicine from the National Institutes of Health.

Gregory Meloni, MSE: Receives salary support from grants provided to the Icahn School of Medicine from the National Institutes of Health.

Christina Chon, MS: Receives salary support from grants provided to the Icahn School of Medicine from the National Institutes of Health.

John Crary, MD PhD: Receives salary support from grants provided to the Icahn School of Medicine from the National Institutes of Health and support for his research programs from Genentech-Roche.

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Morgello, S., Jacobs, M., Murray, J. et al. Alzheimer’s disease neuropathology may not predict functional impairment in HIV: a report of two individuals. J. Neurovirol. 24, 629–637 (2018). https://doi.org/10.1007/s13365-018-0663-z

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