Evidence map›Paper›PMID 39559926›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Homocysteine, neurodegenerative biomarkers, and APOE ε4 in neurodegenerative diseases.

William Z Lin, Di Yu, Lisa Y Xiong, Julia Zebarth, Ruoding Wang, Corinne E Fischer, Tarek K Rajji, David F Tang-Wai, Carmela Tartaglia, Gustavo Saposnik and 23 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
–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

8 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Higher vitamin BAlzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Homocysteine, neurodegenerative biomarkers, and APOE ε4 in neurodegenerative diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    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

33 authors.

William Z LinDepartment of Pharmacology & Toxicology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0002-3610-5213
Di YuDepartment of Pharmacology & Toxicology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Lisa Y XiongDepartment of Pharmacology & Toxicology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Julia ZebarthDepartment of Pharmacology & Toxicology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Ruoding WangDepartment of Pharmacology & Toxicology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Corinne E FischerDepartment of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Tarek K RajjiToronto Dementia Research Alliance, University of Toronto, Toronto, Ontario, Canada.
David F Tang-WaiKrembil Brain Institute, University Health Network, Toronto, Ontario, Canada.
Carmela TartagliaTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
Gustavo SaposnikStroke Outcomes and Decision Neuroscience Research Unit, Division of Neurology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Richard H SwartzHurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
David A GrimesDivision of Neurology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Anthony E LangDivision of Neurology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Robert A HegeleSchulich School of Medicine & Dentistry, Western University, London, Ontario, Canada.
Sali FarhanRobarts Research Institute, Western University, London, Ontario, Canada.
Joel RamirezHurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Sean SymonsHurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Maged GoubranHurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Malcolm A BinnsRotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada.
Wendy LouDepartment of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
Roger A DixonDepartment of Psychology, Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada.
Joseph B OrangeSchool of Communication Sciences and Disorders, Western University, London, Ontario, Canada.
Angela C RobertsSchool of Communication Sciences and Disorders, Western University, London, Ontario, Canada.
Angela K TroyerDepartment of Psychology, University of Toronto, Toronto, Ontario, Canada.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Nathan HerrmannHurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Jennifer S RabinHurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Bradley J MacIntoshHurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Mario MasellisHurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Krista L LanctôtDepartment of Pharmacology & Toxicology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Sandra E BlackHurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Walter SwardfagerDepartment of Pharmacology & Toxicology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0002-0030-8908
ONDRI Investigators

Funding

AD Strategic FundAlzheimer Drug Discovery Foundation 201809-2016862Alzheimer's Association ADSF-21-831376-CAlzheimer's Association ADSF-21-831377-CAlzheimer's Association ADSF-21-831381-CBaycrest FoundationBluefield ProjectBruyère Research InstituteCanada Graduate Scholarships 202111FBD-476226Canada Research Chairs Program CRC-2020-00353Centre for Addiction and Mental Health FoundationErling-Persson Family FoundationEuropean Union Joint Programme - Neurodegenerative Disease Research JPND2021-00694European Union's Horizon 2020 research and innovation 860197 (MIRIADE)European Union's Horizon Europe research and innovation programme 101053962Hjärnfonden FO2022-0270London Health Sciences FoundationMcMaster University Faculty of Health SciencesNational Institute for Health and Care Research University College London Hospitals Biomedical Research CentreOlav Thon FoundationOntario Brain InstituteOntario Ministry of Colleges and Universities ER21-16-141Ottawa Brain and Mind Research InstituteQueen's University Faculty of Health SciencesStiftelsen för Gamla TjänarinnorSwedish Research Council 2019-02397Swedish Research Council 2022-01018Swedish Research Council 2023-00356Swedish State Support for Clinical Research ALFGBG-71320Temerty Family FoundationThunder Bay Regional Health Sciences CentreUK Dementia Research Institute UKDRI-1003University of Ottawa Faculty of MedicineWindsor/Essex County ALS Association
6 · The paper itself

Abstract

introductionElevated plasma homocysteine (Hcy) is associated with an increased risk of developing neurodegenerative diseases; however, its relationship with the apolipoprotein E (APOE) ε4 allele has not been well characterized.

methodsParticipants clinically diagnosed with Alzheimer's disease or mild cognitive impairment (AD/MCI), frontotemporal dementia, Parkinson's disease, or cerebrovascular disease were stratified by the presence of the APOE ε4 allele. Volumetric magnetic resonance imaging, plasma amyloid/tau/neurodegeneration biomarkers, and cognitive performance were quantified.

resultsAcross all diagnostic groups, Hcy was associated with lower brain parenchymal fraction and greater neurofilament light chain in APOE ε4 non-carriers only. In AD/MCI, Hcy was associated with phosphorylated tau 217 in APOE ε4 non-carriers, but not in carriers. Exploratory analyses revealed interactions between Hcy and APOE ε4 on memory and visuospatial function. DISCUSSION: Hcy may contribute to neurodegeneration depending on the presence of the APOE ε4 allele and specific disease processes. Trials on vitamin B12 supplementation may consider stratifying by APOE genotype. Highlights Homocysteine (Hcy) was associated with neurodegenerative biomarkers across disease groups. Relationships with Hcy were predominantly found in apolipoprotein E (APOE) ε4 non-carriers. In Alzheimer's disease, associations between Hcy and phosphorylated tau 217 were found in APOE ε4 non-carriers only. Significant interactions existed between Hcy and APOE ε4 status on cognition.

Indexed as

Apolipoprotein E4HomocysteineNeurodegenerative DiseasesAgedAged, 80 and overAlzheimer DiseaseBiomarkersBrainCognitive DysfunctionFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedParkinson Diseasetau ProteinsApolipoprotein E4BiomarkersHomocysteinetau ProteinsAlzheimer's diseaseapolipoprotein Ebiomarkerscerebrovascular diseasedementiafrontotemporal dementiahomocysteinemild cognitive impairmentParkinson's disease

Identifiers

PMID39559926
PMCPMC11775453

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

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.