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      Neopterin is associated with hippocampal subfield volumes and cognition in HIV

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objective

          HIV infection sets off an immediate immune response and inflammatory cascade that can lead to neuronal injury and cognitive impairment, but the relationship between immune markers, regional brain volumes, and cognition remains understudied in HIV-infected adults.

          Methods

          Cross-sectional associations were examined between serum immune markers of activation (neopterin) and inflammation (interleukin [IL]-1β, IL-6, tumor necrosis factor alpha, and C-reactive protein) with regional brain volumes (cortical, subcortical, total gray matter, hippocampus, and subfields) and cognition in 66 HIV-infected, virally suppressed, adults who underwent 3.0-T MRI as part of the Research Core of the Rush Center of Excellence on Disparities in HIV and Aging. Immune markers were assayed from frozen plasma, values were entered into linear regression models as predictors of regional brain volumes, and interactive effects of immune response and regional brain volumes on cognition were examined.

          Results

          No inflammatory marker was associated with any regional brain volume. Higher neopterin level was associated with lower total hippocampal, presubiculum, and cornu ammonis (CA) subfield volumes. Higher neopterin level and lower total hippocampal volume were independently associated with lower episodic memory, and neopterin level fully mediated the effect of hippocampal atrophy on episodic memory. Higher neopterin levels were associated with lower presubiculum, CA1, and CA4/dentate volumes and lower semantic memory, working memory, and global cognition.

          Conclusion

          Immune activation in response to HIV infection, measured by neopterin, has a deleterious and targeted effect on regional brain structure, which can be visualized with clinically available MRI measures of hippocampus and its subfields, and this effect is associated with lower cognitive function.

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          Most cited references28

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          Race and gender differences in C-reactive protein levels.

          D McGuire, W Vongpatanasin, S. Das … (2005)
          This study sought to determine whether there are race and gender differences in the distribution of C-reactive protein (CRP) levels. Few data are available comparing CRP distributions in different race and gender groups. Recent clinical practice recommendations for CRP testing for cardiovascular risk assessment suggest a uniform threshold to define high relative risk (>3 mg/l). We measured CRP in 2,749 white and black subjects ages 30 to 65 participating in the Dallas Heart Study, a multiethnic, population-based, probability sample, and compared levels of CRP between different race and gender groups. Black subjects had higher CRP levels than white subjects (median, 3.0 vs. 2.3 mg/l; p 3 mg/l was 31%, 40%, 51%, and 58% in white men, black men, white women, and black women, respectively (p 3 mg/l remained more common in white women (odds ratio [OR] 1.6; 95% confidence interval [CI] 1.1 to 2.5) and black women (OR 1.7; 95% CI 1.2 to 2.6) but not in black men (OR, 1.3; 95% CI, 0.8 to 1.9) when compared with white men. Significant race and gender differences exist in the population distribution of CRP. Further research is needed to determine whether race and gender differences in CRP levels contribute to differences in cardiovascular outcomes, and whether thresholds for cardiovascular risk assessment should be adjusted for different race and gender groups.
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            Kynurenine and its metabolites in Alzheimer's disease patients.

            E Gulaj, K. Pawlak, B Bien … (2010)
            The kynurenine pathway (KP) is a major route of tryptophan metabolism. Several metabolites of this pathway are proposed to be involved in the pathogenesis of Alzheimer's disease. The aim of this study was to evaluate peripheral KP in patients with Alzheimer type dementia and a detailed analysis of correlation between kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), anthranilic acid (AA), quinolinic acid (QUIN) and degree of neuropsychological changes in AD. The plasma concentration of tryptophan and its products degradation by kynurenine pathway were analyzed in 34 patients suffering from Alzheimer type dementia and 18 controls in similar age using high-performance liquid chromatography technique. In demented patients we found lower tryptophan and KYNA concentrations. There was a non-significant increase of KYN, 3-HK and AA levels, and a Marked increase of QUIN in Alzheimer's disease group. We observed positive correlations between cognitive function tests and plasma KYNA levels, and inversely correlations between these tests and QUIN levels in Alzheimer type dementia. Increased TRP degradation and simultaneous altered kynurenines levels were found in plasma of AD patients. It proves activation of peripheral kynurenine pathway in this type of dementia. The alterations of two main KYN metabolites: KYNA and QUIN seem to be associated with the impairment of the cognitive function in AD patients. This appears to offer Novel therapeutic opportunities, with the development of new compounds as a promising perspective for brain neuroprotection.
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              Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma

              J Troppmair, D. Niederwieser, P. Swetly … (1984)
              Neopterin, a compound derived from GTP, represents a precursor molecule of biopterin that is an essential cofactor in neurotransmitter synthesis. We have recently reported that in vivo as well as in vitro immune responses are accompanied by an increased release of neopterin and that this phenomenon can be used for the biochemical monitoring of diseases accompanied by hyperimmune stimulation. This article deals with the cellular origin and the control of this immune response- associated neopterin release in vitro. Using highly purified or monoclonal cellular reagents we demonstrate that macrophages (M phi) stimulated with supernatants from activated T cells release large amounts of neopterin into culture supernatants. Further experiments involving induction of neopterin release from M phi with various human recombinant interferons (IFNs) or neutralization of the effect of T cell supernatants with various monoclonal anti-IFN antibodies revealed immune IFN as the active principle. It thus appears that a metabolic pathway so far exclusively known in context with the generation of an essential cofactor of neurotransmitter-synthesis during immune responses is also activated in M phi under stringent control by immune IFN-like lymphokines.
              Article 0 comments Cited 101 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Debra A. Fleischman:
                Comment :

                Scientific Advisory Boards:

                1. NONE

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. NONE

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. National Institute of Minority Health and Health Disparities grant P20MD6886 5/25/12-1/31/18. Role: Co-Principal Investigator with K. Arfanakis. Project 1: Combined Effects of HIV, age and race on inflammation-related brain abnormalities

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Konstantinos Arfanakis:
                Comment :

                Scientific Advisory Boards:

                1. NONE

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. NONE

                Editorial Boards:

                1. Brain Imaging and Behavior

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. National Institute of Aging, R01AG052200, PI, 2016-2021 National Institute of Neurological Disorders and Stroke, UH2NS100599, Multi-PI, 2016-2018

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Sue Leurgans:
                Comment :

                Scientific Advisory Boards:

                1. NONE

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. NONE

                Editorial Boards:

                1. (1) Neurology, Associate Editor for Statistics, 2015-

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. (1) NIH: P30 AG010161 (ADC), core Leader and statistician, 2007-present (2) NIH: R01 AG042210, statistician, 2011-present (3) NIH: R01 NS078009, statistician, 2012-present (4) NIH: P20 MD006886, statistician 2013-present (5) NIH: RF1 AG015819, statisician, 2015-present (6) NIH: U02 AG046152-S1, statisician, 2015-present (7) NIH R01 AG034374, statistician, 2015-present (8) NIH: R01 AG047976, statistician, 2014-present (9) NIH: R01 AG033570, statistician, 2015-present

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Sheila M. Keating:
                Comment :

                Scientific Advisory Boards:

                1. NONE

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. NONE

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. 1) NIH/NHLBI; R01 HL121232-01A1, Scientist? 2) NIH/NIAID; R44AI098567, Scientist? 3) NIH/NHLBI; HHSN268201100001I and HHSN268201100007I; Staff Scientist; 4) NIH/NIAID; HHSN272201000045C; Staff Scientist; 5) US FDA; HHSF223201510149C; Staff Scientist; 6) NIH/NINDS, 1R01NS094067-01A1; Investigator.

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. 1) OPP1115400; Scientist; 2) amfAR Institute for HIV Cure; 501132.

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Melissa Lamar:
                Comment :

                Scientific Advisory Boards:

                1. NONE

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. NONE

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. (1) National Institute on Aging, R21AG048176 (PI), 9/1/15-3/31/18 (2) National Institute on Aging, P30AG010161 (PI of pilot grant), 7/1/16-6/30/18 (3) National Institute of Neurological Disorders and Stroke, R21NS095723 (co-I) 8/1/16-7/30/18 (4) National Institute on Aging, R01AG033678 (co_I), 9/15/09-4/30/20 (5) National Institute on Aging, R01AG029672 (co-I), 5/1/17-11/30/21 (6) National Heart, Lung, and Blood Institute, R01HL129153(co-I), 4/1/16-3/31/21 (7) NINDS, UH2NS100599 (co-I), 9/30/16-7/31/18 Completed Research Support NIA, K01AG040192 (PI) 4/1/12-3/31/17

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                David A. Bennett:
                Comment :

                Scientific Advisory Boards:

                1. (1) Vigorous Minds, Scientific Advisory Board; (2) Takeda Pharm - Adjudication committee AD4833/TOMM40_301 study; (3) AbbVie - Data Monitoring Committee; (4) EABs: India Institute of Science; MCSA; Columbia ADRC; CCNA; CIMA-Q, WFU, Emory, MODEL-AD, REGARDS; (5) DMCs: HRS, MIDUS; (6) National Advisory Council on Aging.

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. NONE

                Editorial Boards:

                1. (1) Neurology, Editorial Board; (2) Current Alzheimer Research, Editorial Board; (3) Neuroepidemiology, Editorial Board.

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NIH: P30AG10161, PI; RF1AG15819, PI; R01AG17917, PI; R01AG36042, PI; R01AG54058, PI; U01AG46152, MPI; U01AG46161, MPI; R01AG33678, co-I; R01AG34374, co-I.

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Oluwatoyin M. Adeyemi:
                Comment :

                Scientific Advisory Boards:

                1. NONE

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                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. NONE

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. 1. Gilead

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. 1. Abbvie- research support

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

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                1. NONE

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                1. NONE

                Legal Proceedings:

                1. NONE

                Lisa L. Barnes:
                Comment :

                Scientific Advisory Boards:

                1. NONE

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. NONE

                Editorial Boards:

                1. Journal of Aging And Health, member of editorial board, 2006 - present. No compensation received.

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. (1) NIA, P30-AG10161, PI of Clinical Core; (2) NIA, RF1-AG22018, PI; (3) NIMHD,P20-MD6886, PI; (4) NIA, P30AG17917, Co-I; (5) NIA, RF1AG51641, Co-I; (6) NIA, U2CAAG54397, Co-I; (7) NIA, R01AG51635, Co-I; (8) NIA, R01AG52583, Co-I; (9) NIA, RF1AG54057, Co-I.

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

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                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

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                Journal
                Journal ID (nlm-ta): Neurol Neuroimmunol Neuroinflamm
                Journal ID (iso-abbrev): Neurol Neuroimmunol Neuroinflamm
                Journal ID (hwp): nnn
                Journal ID (publisher-id): NEURIMMINFL
                Title: Neurology® Neuroimmunology & Neuroinflammation
                Publisher: Lippincott Williams & Wilkins (Hagerstown, MD )
                ISSN (Electronic): 2332-7812
                Publication date (Electronic): 11 June 2018
                Publication date Collection: July 2018
                Publication date PMC-release: 11 June 2018
                Volume: 5
                Issue: 4
                Electronic Location Identifier: e467
                Affiliations
                From the Rush Alzheimer's Disease Center (D.A.F., K.A., S.L., M.L., D.A.B., L.L.B.), Rush University Medical Center; the Department of Neurological Sciences (D.A.F., S.L., M.L., D.A.B., L.L.B.), the Department of Behavioral Sciences (D.A.F., M.L., L.L.B.), the Department of Preventive Medicine (S.L.), the Department of Diagnostic Radiology and Nuclear Medicine (K.A.), Rush University Medical Center; Ruth M. Rothstein CORE Center (O.M.A.); the Biomedical Engineering (K.A.), Illinois Institute of Technology, Chicago; the Blood Systems Research Institute (S.M.K.), San Francisco, CA; and the University of California at San Francisco (S.M.K.), Laboratory Medicine.
                Author notes
                Correspondence Dr. Fleischman debra_fleischman@ 123456rush.edu

                Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NN.

                The Article Processing Charge was funded by the authors.

                Article
                Publisher ID: NEURIMMINFL2017014860
                DOI: 10.1212/NXI.0000000000000467
                PMC ID: 5999345
                SO-VID: 3a3f1850-118e-4eee-a719-995de636b3ce
                Copyright © Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

                History
                Date received : 16 October 2017
                Date accepted : 04 April 2018
                Funding
                Funded by: National Institute of Aging
                Award ID: P30AG010161
                Categories
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                Subject: 25
                Subject: 130
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                Subject: Article
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