Evidence map›Paper›PMID 41421353›Full record

ArticleCell reports. Medicine2026

Blood measure of neuronal death is exponentially higher with age, especially in females, and halted in Alzheimer's disease by GM-CSF treatment.

Stefan H Sillau, Christina Coughlan, Md Mahiuddin Ahmed, Kavita Nair, Paula Araya, Matthew D Galbraith, Alanna Ritchie, Athena Ching-Jung Wang, Mihret T Elos, Brianne M Bettcher and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Can we refute a role for infections in Alzheimer's disease pathogenesis?Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
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

15 authors.

Stefan H SillauDepartment of Neurology and the University of Colorado Alzheimer's and Cognition Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Christina CoughlanDepartment of Neurology and the University of Colorado Alzheimer's and Cognition Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Linda Crnic Institute for Down Syndrome, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Md Mahiuddin AhmedDepartment of Neurology and the University of Colorado Alzheimer's and Cognition Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Linda Crnic Institute for Down Syndrome, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Kavita NairDepartment of Neurology and the University of Colorado Alzheimer's and Cognition Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Clinical Pharmacy, Center for Pharmaceutical Outcomes Research (CePOR), University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Paula ArayaLinda Crnic Institute for Down Syndrome, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Matthew D GalbraithLinda Crnic Institute for Down Syndrome, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Alanna RitchieDepartment of Neurology and the University of Colorado Alzheimer's and Cognition Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Athena Ching-Jung WangDepartment of Neurology and the University of Colorado Alzheimer's and Cognition Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Linda Crnic Institute for Down Syndrome, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Mihret T ElosDepartment of Neurology and the University of Colorado Alzheimer's and Cognition Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Linda Crnic Institute for Down Syndrome, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Brianne M BettcherDepartment of Neurology and the University of Colorado Alzheimer's and Cognition Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Joaquin M EspinosaLinda Crnic Institute for Down Syndrome, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Heidi J ChialDepartment of Neurology and the University of Colorado Alzheimer's and Cognition Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Linda Crnic Institute for Down Syndrome, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Neill EppersonDepartment of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Timothy D BoydDepartment of Neurology and the University of Colorado Alzheimer's and Cognition Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Linda Crnic Institute for Down Syndrome, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Huntington PotterDepartment of Neurology and the University of Colorado Alzheimer's and Cognition Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Linda Crnic Institute for Down Syndrome, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA. Electronic address: huntington.potter@cuanschutz.edu.

Funding

Phase II trial of GM-CSF/sargramostim in Alzheimer's DiseaseR01AG071151 · NIA · UNIVERSITY OF COLORADO DENVER · PI Huntington Potter · 2021 to 2026
$7.5M
NIA NIH HHS R01 AG071151
6 · The paper itself

Abstract

Aging increases the risk of neurodegeneration, cognitive decline, and Alzheimer's disease (AD). We report that plasma concentrations of ubiquitin C-terminal hydrolase-L1 (UCH-L1) and neurofilament light (NfL) become exponentially higher from ages 2 to 85 in cross-sectional samples, serving as neuronal death/damage biomarkers across the lifespan. UCH-L1 concentrations rise faster in females, who exhibit increased AD risk. Glial fibrillary acidic protein (GFAP) concentrations increase exponentially after age 40, especially in females. Age-adjusted UCH-L1, NfL, and GFAP plasma concentrations are greatly elevated in mildly cognitively impaired participants. Treatment of human AD trial participants with granulocyte-macrophage colony-stimulating factor (GM-CSF/sargramostim) apparently halts neuronal cell death: UCH-L1 biomarker concentrations are reduced to those of 5-year-old healthy controls. GM-CSF treatment also reduces neuronal apoptosis and astrogliosis in a rat model of AD. An exponential increase in neurodegeneration with age, accelerated by astrogliosis/inflammation, may underlie the contribution of aging to cognitive decline and AD and can be halted by GM-CSF/sargramostim treatment.

Indexed as

AgingAlzheimer DiseaseGranulocyte-Macrophage Colony-Stimulating FactorNeuronsAdolescentAdultAgedAged, 80 and overAnimalsApoptosisBiomarkersCell DeathChildChild, PreschoolDisease Models, AnimalFemaleBiomarkersGlial Fibrillary Acidic ProteinGranulocyte-Macrophage Colony-Stimulating Factorneurofilament protein LNeurofilament ProteinsUbiquitin ThiolesteraseUCHL1 protein, humanagingAlzheimer’scolony-stimulating factor 2glial fibrillary acidic proteingranulocyte-macrophage colony-stimulating factorneurodegenerationneurofilament lightneuroprotectionsenolysisubiquitin C-terminal hydrolase-L1

Identifiers

PMID41421353
PMCPMC12866173

What OpenQuestion holds

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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.