Evidence map›Paper›PMID 26637429›Full record

ArticleJournal of neurovirology2016

Multilevel analysis of neuropathogenesis of neurocognitive impairment in HIV.

Andrew J Levine, Virawudh Soontornniyomkij, Cristian L Achim, Eliezer Masliah, Benjamin B Gelman, Janet S Sinsheimer, Elyse J Singer, David J Moore

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neurovirology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 2 pooled it
2.2field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 71 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  4. Article
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  12. HIV-1 Tat Upregulates TREM1 Expression in Human Microglia.Journal of immunology (Baltimore, Md. : 1950) · 2023
    Article
  13. Article
  14. Review
  15. Serum inflammation markers associated with altered brain white matter microstructure in people with HIV on antiretroviral treatment.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Andrew J LevineDepartment of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA. ajlevine@mednet.ucla.edu.
Virawudh SoontornniyomkijDepartment of Psychiatry, University of California San Diego School of Medicine, La Jolla, CA, USA.
Cristian L AchimDepartments of Psychiatry and Pathology, University of California San Diego School of Medicine, La Jolla, CA, USA.
Eliezer MasliahDepartments of Neurosciences and Pathology, University of California San Diego School of Medicine, La Jolla, CA, USA.
Benjamin B GelmanDepartment of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
Janet S SinsheimerDepartments of Human Genetics and Biomathematics, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
Elyse J SingerDepartment of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
David J MooreDepartment of Psychiatry, University of California San Diego School of Medicine, La Jolla, CA, USA.
University of California, San Diego · USUniversity of California, Los Angeles · USThe University of Texas Medical Branch at Galveston · US

Funding

STRUCTURAL NEUROIMAGING COREP30MH062512 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DAVID J MOORE · 2001 to 2026
$50.4M
YALE CENTER FOR THE: LEARNING &ATTENTIONP41RR013642 · NCRR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEARER, ELAINE L · 1998 to 2011
$21.9M
California NeuroAIDS Tissue NetworkU24MH100928 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ACHIM, CRISTIAN L, MOORE, DAVID J · 2013 to 2023
$13.9M
NEUROAIDS TISSUE NETWORKR24MH059745 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GRANT, IGOR · 1998 to 2007
$13.2M
NATIONAL NEUROLOGICAL AIDS BANKU24MH100929 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SINGER, ELYSE J · 2013 to 2023
$12.5M
Texas NeuroAIDS Research CenterU24MH100930 · NIMH · UNIVERSITY OF TEXAS MED BR GALVESTON · PI GELMAN, BENJAMIN B. · 2013 to 2023
$12.1M
National Neurological AIDS Bank (NNAB)R24NS038841 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SINGER, ELYSE J · 1998 to 2007
$12.0M
STATISTICAL METHODS FOR GENE MAPPINGR01GM053275 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LANGE, KENNETH L · 1995 to 2019
$9.3M
National Neurological AIDS BankU01MH083500 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SINGER, ELYSE J · 2008 to 2012
$7.2M
Brain Amyloid and HAND in the cART eraR01MH105319 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ACHIM, CRISTIAN L · 2015 to 2019
$2.5M
A multi-systems study of HIV neuropathogenesis: genetics-neuropathology-behaviorR01MH096648 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LEVINE, ANDREW J, MOORE, DAVID J · 2012 to 2016
$1.6M
NCRR NIH HHS P41 RR013642NIGMS NIH HHS R01 GM053275NIMH NIH HHS N01 MH032002NIMH NIH HHS P30 MH062512NIMH NIH HHS R01 MH096648NIMH NIH HHS R01 MH105319NIMH NIH HHS R24 MH059745NIMH NIH HHS U01 MH083500NIMH NIH HHS U24 MH100928NIMH NIH HHS U24 MH100929NIMH NIH HHS U24 MH100930NINDS NIH HHS R24 NS038841
6 · The paper itself

Abstract

The neuropathogenesis of HIV-associated neurocognitive disorders (HAND) remains puzzling. We interrogated several levels of data (host genetic, histopathology, brain viral load, and neurocognitive) to identify histopathological changes most relevant to HAND. The design of the study is a clinicopathological study employing genetic association analyses. Data and brain tissue from 80 HIV-infected adults were used. Markers in monocyte chemoattractant protein-1 (MCP-1), interleukin 1-alpha (IL1-α), macrophage inflammatory protein 1-alpha (MIP1-α), DRD3, DRD2, and apolipoprotein E (ApoE) were genotyped. Microtubule associated protein 2 (MAP2), synaptophysin (SYP), human leukocyte antigen-DR (HLA-DR), glial fibrillary acidic protein (GFAP), amyloid beta (A-Beta), and ionized calcium-binding adaptor molecule-1 (Iba-1) immunoreactivity were quantified in the frontal cortex, putamen, and hippocampus. A composite score for each marker (mean of the three brain regions) was used. Neurocognitive functioning and other clinical variables were determined within 1 year of death. Brain HIV RNA viral load was available for a subset of cases. MAP2 and SYP proved most relevant to neurocognitive functioning. Immunoreactivity of these markers, as well as A-Beta and Iba-1, was correlated with brain HIV RNA viral load. Several genetic markers in combination with other factors predicted histopathology: HIV blood viral load, MIP1-α genotype, and DRD3 genotype predicted Iba-1 immunoreactivity; the duration of infection and IL1-α genotype predicted GFAP immunoreactivity; ApoE genotype and age at death predicted A-Beta immunoreactivity. These data indicate that HIV replication in the brain is the primary driving force leading to neuroinflammation and dysfunctional protein clearance, as reflected by A-Beta and Iba-1. Downstream to these changes are synaptodendritic degeneration, which is the immediate histopathological substrate of the neurocognitive impairment characteristic of HAND. These intermediate histopathological phenotypes are influenced by host genetic polymorphisms in genes encoding cytokines/chemokines, neuronal protein clearance pathways, and dopaminergic factors.

Indexed as

Multilevel AnalysisVirus ReplicationAdaptor Proteins, Signal TransducingAdultAIDS Dementia ComplexAmyloid beta-PeptidesBiomarkersCalcium-Binding ProteinsChemokine CCL2DNA-Binding ProteinsFemaleFrontal LobeGene ExpressionHippocampusHumansInterleukin-1alphaAdaptor Proteins, Signal TransducingAIF1 protein, humanAmyloid beta-PeptidesBiomarkersCalcium-Binding ProteinsCCL2 protein, humanChemokine CCL2DNA-Binding ProteinsIL1A protein, humanInterleukin-1alphaMAP2 protein, humanMAPKAP1 protein, humanMicrofilament ProteinsMicrotubule-Associated ProteinsReceptors, DopamineSynaptophysinSYP protein, humanHistopathologyHIVHIV-associated neurocognitive disordersHost geneticNeuroAIDSSynaptodendritic

Identifiers

PMID26637429
PMCPMC4893344
OpenAlexW2187648708

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.