Evidence map›Paper›PMID 41266593›Full record

ArticleCommunications medicine2025

APOE ε4 potentiates tau related reactive astrogliosis assessed by cerebrospinal fluid YKL40 in Alzheimer's disease.

Lydia Trudel, Joseph Therriault, Arthur C Macedo, Marcel S Woo, Nesrine Rahmouni, Étienne Aumont, Stijn Servaes, Seyyed Ali Hosseini, João Pedro Ferrari-Souza, Bruna Bellaver and 22 more

Abstract read
In one paragraph

Article in Communications medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

32 authors.

Lydia TrudelTranslational Neuroimaging Laboratory Department of Neurology and Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada. lydia.trudel@mail.mcgill.ca.ORCID http://orcid.org/0009-0002-5593-7717
Joseph TherriaultTranslational Neuroimaging Laboratory Department of Neurology and Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.ORCID http://orcid.org/0000-0002-7826-4781
Arthur C MacedoTranslational Neuroimaging Laboratory Department of Neurology and Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Marcel S WooTranslational Neuroimaging Laboratory Department of Neurology and Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.ORCID http://orcid.org/0000-0002-1306-2708
Nesrine RahmouniTranslational Neuroimaging Laboratory Department of Neurology and Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Étienne AumontTranslational Neuroimaging Laboratory Department of Neurology and Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Stijn ServaesTranslational Neuroimaging Laboratory Department of Neurology and Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Seyyed Ali HosseiniTranslational Neuroimaging Laboratory Department of Neurology and Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.ORCID http://orcid.org/0000-0001-7542-7541
João Pedro Ferrari-SouzaDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0003-2183-1551
Bruna BellaverDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Pamela L FerreiraDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0003-2134-9829
Tevy ChanTranslational Neuroimaging Laboratory Department of Neurology and Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.ORCID http://orcid.org/0009-0001-9134-5949
Yi-Ting WangTranslational Neuroimaging Laboratory Department of Neurology and Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.ORCID http://orcid.org/0000-0002-9130-5461
Jaime Fernandez-AriasTranslational Neuroimaging Laboratory Department of Neurology and Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Yansheng ZhengTranslational Neuroimaging Laboratory Department of Neurology and Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Brandon HallTranslational Neuroimaging Laboratory Department of Neurology and Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.ORCID http://orcid.org/0009-0007-4578-2033
Jenna StevensonTranslational Neuroimaging Laboratory Department of Neurology and Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Robert HopewellPET Unit, McConnell Brain Imaging Centre, Montréal, QC, Canada.
Chris Hung-Hsin HsiaoPET Unit, McConnell Brain Imaging Centre, Montréal, QC, Canada.ORCID http://orcid.org/0009-0009-2062-3516
Maxime MontembeaultTranslational Neuroimaging Laboratory Department of Neurology and Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.ORCID http://orcid.org/0000-0002-9369-0498
Jesse KlostranecDepartment of Diagnostic Radiology, Faculty of Medicine, McGill University, Montreal, QC, Canada.
Yasser Iturria-MedinaDepartment of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, QC, Canada.ORCID http://orcid.org/0000-0002-9345-0347
Paolo VitaliTranslational Neuroimaging Laboratory Department of Neurology and Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.ORCID http://orcid.org/0000-0001-8953-1542
Thomas K KarikariDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.ORCID http://orcid.org/0000-0003-1422-4358
Andrea L BenedetDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Nicholas J AshtonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
Eduardo ZimmerGraduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Serge GauthierTranslational Neuroimaging Laboratory Department of Neurology and Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Tharick A PascoalDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0001-9057-8014
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.ORCID http://orcid.org/0000-0002-1890-4193
Pedro Rosa-NetoTranslational Neuroimaging Laboratory Department of Neurology and Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada. pedro.rosa@mcgill.ca.ORCID http://orcid.org/0000-0001-9116-1376

Funding

Plasma brain-derived tau: a novel Alzheimer’s disease-type neurodegeneration biomarker with potential to complete the AT(N) scheme in bloodR01AG083874 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Thomas K Karikari · 2023 to 2026
$14.5M
Alzheimer's Association NIRG-12-92090, NIRP-12-259245NIA NIH HHS R01 AG083874
6 · The paper itself

Abstract

backgroundGlial responses are involved in neurodegenerative processes, with tau pathology often associated with increased glial inflammatory responses in Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele, the major genetic susceptibility gene for AD, might contribute to this process by modulating both tau pathology and inflammatory cascades in the brain.

methodsWe used data from the Translational Biomarkers of Alzheimer's Disease (TRIAD) cohort (n = 137) to investigate the association between YKL-40, a marker of reactive astrogliosis, and tau burden measured with PET imaging, while also exploring the involvement of APOE ε4 carriership. Statistical analyses included correlation and regression models controlling for age and sex.

resultsHere we show that tau pathology is positively associated with YKL-40 levels, reflecting regional patterns of astrocyte activity in the brain. Furthermore, this association is more widespread in individuals carrying the APOE ε4 allele, suggesting a genotype-specific modulation of the glial neuroinflammatory response.

conclusionsOur findings demonstrate a link between tau accumulation and astrocyte-mediated neuroinflammation in AD and highlight the modulatory role of APOE ε4 in this process. Taken together, our findings help inform the multifaceted role of tau-associated neuroinflammation in the progression of AD.

Identifiers

PMID41266593
PMCPMC12635130

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.