Evidence mapPaperPMID 41205698Full record

ArticleJournal of lipid research2025

Exploring biomarkers of neurodegenerative risk: associations of oxysterols, sex hormones, and reproductive characteristics in older women.

Michelle M Dunk, Ljerka Delac, Stephen R Rapp, Ira Driscoll, Maria Latorre-Leal, Leslie V Farland, Bernhard Haring, Holly R Harris, Su Yon Jung, JoAnn E Manson and 6 more

Abstract read
In one paragraph

Article in Journal of lipid research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

16 authors.

Michelle M DunkAging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Division of Neurogeriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden. Electronic address: michelle.dunk@ki.se.
Ljerka DelacDivision of Neurogeriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Stephen R RappDepartment of Psychiatry & Behavioral Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Ira DriscollWisconsin Alzheimer's Disease Research Center, Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Maria Latorre-LealDivision of Neurogeriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Leslie V FarlandDepartment of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA.
Bernhard HaringDepartment of Medicine III, Saarland University, Homburg, Saarland, Germany; Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
Holly R HarrisProgram in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Su Yon JungDepartment of Epidemiology, Fielding School of Public Health, Translational Sciences Section, Jonsson Comprehensive Cancer Center, School of Nursing, University of California, Los Angeles, CA, USA.
JoAnn E MansonDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Heather M Ochs-BalcomDepartment of Epidemiology and Environmental Health, School of Public Health and Health Professions, State University of New York at Buffalo, Buffalo, NY, USA.
Aladdin H ShadyabHerbert Wertheim School of Public Health and Human Longevity Science and Division of Geriatrics, Gerontology, and Palliative Care, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Julie C WeitlaufSierra Pacific Mental Illness, Research, Education and Clinical Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA; Department of Psychiatry and Behavioral Sciences and, by courtesy, Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA, USA.
Hong XuDivision of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Eric WestmanDivision of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Silvia MaioliDivision of Neurogeriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden. Electronic address: silvia.maioli@ki.se.

Funding

THE PURPOSE OF THIS MODIFICATION IS TO DE-OBLIGATE NHLBI FUNDING FROM THE WOMEN'S HEALTH INITIATIVE (WHI) - CLINICAL COORDINATING CENTER (CCC).75N92021D00001 · FRED HUTCHINSON CANCER CENTER · 2025 to 2025
$9.3M
WOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC): TASK AREA A AND A275N92021D00002 · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2025 to 2025
$1.2M
WOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC): TASK AREA A AND A275N92021D00004 · STANFORD UNIVERSITY · 2025 to 2025
$1.1M
WOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC): TASK AREA A AND A275N92021D00005 · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2025 to 2025
$47k
WOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC): TASK AREA A AND A275N92021D00003 · OHIO STATE UNIVERSITY · 2025 to 2025
$39k
NHLBI NIH HHS 75N92021D00001NHLBI NIH HHS 75N92021D00002WHI NIH HHS 75N92021D00003WHI NIH HHS 75N92021D00004WHI NIH HHS 75N92021D00005
6 · The paper itself

Abstract

Women face a higher lifetime risk of developing neurodegenerative diseases such as Alzheimer's disease and related dementias. The menopausal transition, characterized by a decline in estrogen levels, may affect cholesterol metabolism and neurodegenerative processes. Oxysterols, oxidized cholesterol derivatives, play a role in these pathways, with 24(S)-hydroxycholesterol (24HC) reflecting brain cholesterol turnover and 27-hydroxycholesterol (27HC) linked to systemic cholesterol metabolism. We investigated associations of plasma oxysterols with circulating sex hormones and characteristics of reproductive history in 1,974 postmenopausal women with no history of dementia from the Women's Health Initiative, taking into account APOE4 status and cholesterol-lowering medication. We found that higher levels of bioavailable estradiol were associated with higher 24HC and 27HC levels, and higher estrone was associated with higher 24HC (all P values <0.05). Associations of estradiol with 24HC and 27HC were stronger among APOE4 carriers and those not using cholesterol-lowering medication, with a significant interaction between bioavailable estradiol and APOE4 in relation to 27HC (p for interaction = 0.04). Having an older age at menopause was associated with lower 24HC among those taking cholesterol medication (p for interaction = 0.03). Our findings suggest that 24HC and 27HC may be proxy biomarkers of neuronal health and estrogen status in postmenopausal women. The stronger associations between estradiol and oxysterols among APOE4 carriers and those not using cholesterol medication suggest the need to account for hormonal, genetic, and pharmacological factors when evaluating neurodegenerative risk. Longitudinal studies are warranted to further investigate oxysterols as potential early biomarkers of risk for Alzheimer's disease and related dementias.

Indexed as

Gonadal Steroid HormonesNeurodegenerative DiseasesOxysterolsReproductionAgedAlzheimer DiseaseApolipoprotein E4BiomarkersFemaleHumansHydroxycholesterolsMiddle AgedRisk Factors24-hydroxycholesterol27-hydroxycholesterolApolipoprotein E4BiomarkersGonadal Steroid HormonesHydroxycholesterolsOxysterols24(S)-hydroxycholesterolAlzheimer’s diseaseapolipoprotein EcholesterolCYP46A1estrogenhormoneslipidsreproductive historystatins

Identifiers

PMID41205698
PMCPMC12863040

What Socratic holds

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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.