Evidence map›Paper›PMID 42732855›Full record

Trial reportNeurobiology of disease2026

Matrix metalloproteinase-9 is associated with CX3CL1 on tau and amyloid biomarker pathways in APOE4 carriers.

Aimee K Johnson, Carol A Van Hulle, Hannah Zylstra, Kate Cronin, Kevin Johnson, Leonardo Rivera-Rivera, Richard Chappell, Rachael Wilson, Przemysław R Kac, Carey E Gleason and 4 more

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurobiology of disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02719327 (Impact of Icosapent Ethyl on Alzheimers Disease Biomarkers in Preclinical Adults), which is not on this map. Not yet cited in PubMed.

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

NCT02719327 phase2 / phase3completednot on this map

Impact of Icosapent Ethyl on Alzheimers Disease Biomarkers in Preclinical Adults

TypeinterventionalSponsorVA Office of Research and DevelopmentRan2017 to 2023Enrolled131ConditionsAlzheimer's DiseaseArmsicosapent ethyl (IPE), gel cap placebo
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Aimee K JohnsonNeuroscience Training Program, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA; Institute on Aging, University of Wisconsin-Madison, Madison, WI, USA. Electronic address: akjohnson26@wisc.edu.
Carol A Van HulleWisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Division of Geriatrics, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Hannah ZylstraWisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Division of Geriatrics, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
Kate CroninWisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Division of Geriatrics, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
Kevin JohnsonDepartment of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Leonardo Rivera-RiveraWisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Division of Geriatrics, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Richard ChappellWisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Rachael WilsonWisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Przemysław R KacDepartment of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Carey E GleasonWisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Division of Geriatrics, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
Henrik ZetterbergWisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK; UK Dementia Research Institute at UCL, London, UK; Centre for Brain Research, Indian Institute of Science, Bangalore, India.
Sterling C JohnsonInstitute on Aging, University of Wisconsin-Madison, Madison, WI, USA; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Division of Geriatrics, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Anthony P AugerNeuroscience Training Program, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA; Institute on Aging, University of Wisconsin-Madison, Madison, WI, USA.
Cynthia M CarlssonWisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Division of Geriatrics, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI, USA; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Geriatric Research, Education, and Clinical Center, William S. Middleton Veterans Affairs Hospital, 2500 Overlook Terrace, Madison, WI, USA.

Funding

Wisconsin Alzheimer's Disease Research CenterP30AG062715 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Barbara Brigitta Bendlin · 2019 to 2026
$34.5M
CSRD VA I01 CX001261NIA NIH HHS P30 AG062715
6 · The paper itself

Abstract

APOE ε4 carriers exhibit heightened pro-inflammatory responses and microglial dysregulation compared to non-carriers. CX3CL1 is a biomarker involved in microglial signaling and Alzheimer's disease. It can be cleaved by proteases such as matrix metalloproteinases (MMPs), which are associated with memory and vasculature remodeling. We examined the role of MMP-9 in the pathway involving the association of CX3CL1 with cerebrospinal fluid (CSF) biomarkers for amyloid and tau in APOE ε4 carriers (APOE4+) compared to non-carriers (APOE4-). We further examined the association between APOE4 groups and inflammatory profiles. CSF samples were collected from 115 cognitively unimpaired VA-eligible Veterans enrolled in the Brain Amyloid and Vascular Effects of Eicosapentaenoic Acid (BRAVE) study (NCT02719327). We found that Aβ42 and Aβ42/Aβ40 were lower in APOE4+ carriers compared to non-carriers. Additionally, p-tau217 was higher among APOE4+ participants compared to APOE4- participants; however, p-tau217/tau was not different between carrier groups. In moderated mediation models, MMP-9 mediated the effect of CX3CL1 on Aβ42/Aβ40, p-tau217/tau and p-tau217/Aβ42 among APOE4+ carriers only. Lastly, we found a correlation between CX3CL1 and a composite pro-inflammatory z score, as well as lower ICAM-1 and VCAM-1 baseline levels in the APOE4+ group. However, CX3CL1 correlated with an anti-inflammatory z score in the APOE4- group, suggesting different inflammatory roles of CX3CL1 in APOE4+ carriers vs non-carriers. These findings suggest that the association of MMP-9 and CX3CL1 plays a unique role in tau and amyloid regulation among APOE4+ carriers, and that early dysregulation of immune systems may occur in cognitively unimpaired APOE4+ individuals.

Indexed as

Amyloid beta-PeptidesApolipoprotein E4Chemokine CX3CL1Matrix Metalloproteinase 9tau ProteinsAgedAlzheimer DiseaseBiomarkersFemaleHeterozygoteHumansMaleMiddle AgedPeptide FragmentsAmyloid beta-PeptidesApolipoprotein E4BiomarkersChemokine CX3CL1CX3CL1 protein, humanMAPT protein, humanMatrix Metalloproteinase 9MMP9 protein, humanPeptide Fragmentstau ProteinsAlzheimer's diseaseAPOE ε4Aβ42/Aβ40CX3CL1ICAM-1InflammationMMP-9P-tau217VCAM-1

Identifiers

PMID42732855
PMCPMC13667386

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Registered trials

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.