Plasma Aβ42/Aβ40 Ratios in Older People With Human Immunodeficiency Virus.

Autor:	Cooley SA; Department of Neurology, Washington University in St Louis, St Louis, Missouri, USA., Nelson B; Department of Neurology, Washington University in St Louis, St Louis, Missouri, USA., Boerwinkle A; Department of Neurology, Washington University in St Louis, St Louis, Missouri, USA., Yarasheski KE; C2N Diagnostics, St Louis, Missouri, USA., Kirmess KM; C2N Diagnostics, St Louis, Missouri, USA., Meyer MR; C2N Diagnostics, St Louis, Missouri, USA., Schindler SE; Department of Neurology, Washington University in St Louis, St Louis, Missouri, USA.; Knight Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, Missouri, USA., Morris JC; Department of Neurology, Washington University in St Louis, St Louis, Missouri, USA.; Knight Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, Missouri, USA.; Department of Radiology, Washington University in St Louis, St Louis, Missouri, USA., Fagan A; Knight Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, Missouri, USA., Ances BM; Department of Neurology, Washington University in St Louis, St Louis, Missouri, USA., O'Halloran JA; Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St Louis, Missouri, USA.
Jazyk:	angličtina
Zdroj:	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2023 May 24; Vol. 76 (10), pp. 1776-1783.
DOI:	10.1093/cid/ciad001
Abstrakt:	Background: As people with human immunodeficiency virus (HIV) (PWH) age, it remains unclear whether they are at higher risk for age-related neurodegenerative disorders-for example, Alzheimer disease (AD)-and, if so, how to differentiate HIV-associated neurocognitive impairment from AD. We examined a clinically available blood biomarker test for AD (plasma amyloid-β [Aβ] 42/Aβ40 ratio) in PWH who were cognitively normal (PWH_CN) or cognitively impaired (PWH_CI) and people without HIV (PWoH) who were cognitively normal (PWoH_CN) or had symptomatic AD (PWoH_AD). Methods: A total of 66 PWH (age >40 years) (HIV RNA <50 copies/mL) and 195 PWoH provided blood samples, underwent magnetic resonance imaging, and completed a neuropsychological battery or clinical dementia rating scale. Participants were categorized by impairment (PWH_CN, n = 43; PWH_CI, n = 23; PWoH_CN, n = 138; PWoH_AD, n = 57). Plasma Aβ42 and Aβ40 concentrations were obtained using a liquid chromatography-tandem mass spectrometry method to calculate the PrecivityAD amyloid probability score (APS). The APS incorporates age and apolipoprotein E proteotype into a risk score for brain amyloidosis. Plasma Aβ42/Aβ40 ratios and APSs were compared between groups and assessed for relationships with hippocampal volumes or cognition and HIV clinical characteristics (PWH only). Results: The plasma Aβ42/Aβ40 ratio was significantly lower, and the APS higher, in PWoH_AD than in other groups. A lower Aβ42/Aβ40 ratio and higher APS was associated with smaller hippocampal volumes for PWoH_AD. The Aβ42/Aβ40 ratio and APS were not associated with cognition or HIV clinical measures for PWH. Conclusions: The plasma Aβ42/Aβ40 ratio can serve as a screening tool for AD and may help differentiate effects of HIV from AD within PWH, but larger studies with older PWH are needed. Competing Interests: Potential conflicts of interest. K. E. Y., K. M. K., M. R. M. are full-time employees of and have equity interest in C2N Diagnostics. The PrecivityAD test is licensed by C2N Diagnostics, and Washington University will receive royalties from this test. K. E. Y. and M. R. M. also report royalties or licenses from C2N Diagnostics (equity shares); payment for travel, lodging, and meal expenses to attend scientific meetings as employees of C2N Diagnostics; and a patent planned, issued, or pending for methods for measuring concentrations of biomolecules in biofluids (C2N Diagnostics: US 10,976,323 B2). S. E. S. receives funding from the Barnes-Jewish Hospital Foundation to evaluate the clinical utility of Alzheimer disease blood tests and is an unpaid board member for the Greater Missouri Alzheimer's Association. S. E. S. reports personal honoraria from the University of Wisconsin, St Luke's Hospital, and Houston Methodist Medical Center for presenting lectures, from the University of Washington for serving on the Alzheimer Disease Center Clinical Task Force, and from the University of Indiana for serving on the biospecimen review committee of the National Centralized Repository for Alzheimer's Disease and reports travel support from the National Institute on Aging (grant R01AG070941). S. E. S. also reports that plasma amyloid-β (Aβ) 42/Aβ40 data was provided to Washington University by C2N Diagnostics at no cost. (No payment or research funding were provided by C2N Diagnostics, nor any gifts of financial incentives of any kind to S. E. S.) J. C. M. consults for the Barcelona Brain Research Center and the Native Alzheimer Disease-Related Resource Center in Minority Aging Research (external advisory board); receives honoraria for the Tetra-Institutional Alzheimer Disease Research Center seminar series and Montefiore Grand Rounds; and participates on the data safety monitoring board for the Cure Alzheimer's Fund (strategy council), observational study monitoring board for Diverse VCID (Vascular Contributions to Cognitive Impairment and Dementia), and the Longitudinal early-onset Alzheimer's Disease Study advisory board for Indiana University. J. C. M. also reports National Institutes of Health support, unrelated to the current work (grants P30 AG066444, P01AG003991, P01AG026276, and U19AG032438). A. F. is a member of scientific advisory boards for Roche Diagnostics, Genentech, and DiademRes and consults for DiamiR and Siemens Healthcare Diagnostics. A. F. also reports travel support for in-person attendance at Alzheimer's Association International Conference premeetings in San Diego, California, and travel support/honorarium for in-person attendance at the Scientific Advisory Board meeting for the South Texas Alzheimer's Disease Research Center. B. M. A. is on the data safety monitoring board for Diverse VCID. J. O. H. has received funding from Janssen Scientific for investigator-initiated research, paid to the institution. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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