Evidence map›Paper›PMID 36577365›Full record

ArticleCell reports2022

IGF1 deficiency integrates stunted growth and neurodegeneration in Down syndrome.

Paula Araya, Kohl T Kinning, Christina Coughlan, Keith P Smith, Ross E Granrath, Belinda A Enriquez-Estrada, Kayleigh Worek, Kelly D Sullivan, Angela L Rachubinski, Kristine Wolter-Warmerdam and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 2 pooled it
8.4field-weighted citation impact, top 2% 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

24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 45 citations in OpenAlex.

  1. Blood-based biomarkers for Alzheimer's disease in Down syndrome: A systematic review and meta-analysis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
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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

14 authors at 2 institutions in 1 country.

Paula ArayaLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Kohl T KinningLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Christina CoughlanLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Alzheimer's and Cognition Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Keith P SmithLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Ross E GranrathLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Belinda A Enriquez-EstradaLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Kayleigh WorekLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Kelly D SullivanLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Section of Developmental Biology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Angela L RachubinskiLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Section of Developmental Pediatrics, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Kristine Wolter-WarmerdamSie Center for Down Syndrome, Department of Pediatrics, Children's Hospital Colorado, Aurora, CO 80045, USA.
Francis HickeySie Center for Down Syndrome, Department of Pediatrics, Children's Hospital Colorado, Aurora, CO 80045, USA.
Matthew D GalbraithLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Huntington PotterLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Alzheimer's and Cognition Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Joaquin M EspinosaLinda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: joaquin.espinosa@cuanschutz.edu.
University of Colorado Anschutz Medical Campus · USChildren's Hospital Colorado · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
NIH Prior Approval Process ProfessionalUL1TR002535 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2018 to 2022
$51.1M
Understanding Down Syndrome as an InterferonopathyR01AI150305 · NIAID · UNIVERSITY OF COLORADO DENVER · PI ESPINOSA, JOAQUIN M. · 2019 to 2020
$3.5M
Pre-clinical assessment of JAK inhibitors to ameliorate cytokine storms in Down syndromeR01AI145988 · NIAID · UNIVERSITY OF COLORADO DENVER · PI SULLIVAN, KELLY D. · 2019 to 2023
$2.2M
NCATS NIH HHS UL1 TR002535NCI NIH HHS P30 CA046934NIAID NIH HHS R01 AI145988NIAID NIH HHS R01 AI150305
6 · The paper itself

Abstract

Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), is characterized by stunted growth, cognitive impairment, and increased risk of diverse neurological conditions. Although signs of lifelong neurodegeneration are well documented in DS, the mechanisms underlying this phenotype await elucidation. Here we report a multi-omics analysis of neurodegeneration and neuroinflammation biomarkers, plasma proteomics, and immune profiling in a diverse cohort of more than 400 research participants. We identified depletion of insulin growth factor 1 (IGF1), a master regulator of growth and brain development, as the top biosignature associated with neurodegeneration in DS. Individuals with T21 display chronic IGF1 deficiency downstream of growth hormone production, associated with a specific inflammatory profile involving elevated tumor necrosis factor alpha (TNF-α). Shorter children with DS show stronger IGF1 deficiency, elevated biomarkers of neurodegeneration, and increased prevalence of autism and other conditions. These results point to disruption of IGF1 signaling as a potential contributor to stunted growth and neurodegeneration in DS.

Indexed as

Down SyndromeBiomarkersGrowth DisordersHearing Loss, SensorineuralHumansInsulin-Like Growth Factor IBiomarkersIGF1 protein, humanInsulin-Like Growth Factor IAlzheimer’s diseaseautismCP: Developmental biologyCP: Neurosciencegrowth hormoneinflammationinsulin growth factormecaserminneuroinflammation

Identifiers

PMID36577365
PMCPMC9876612
OpenAlexW4313255504

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.