Evidence map›Paper›PMID 41087722›Full record

ArticleNature aging2025

Cerebrospinal fluid proteomic signatures in cognitively normal individuals identify distinct clusters linked to neurodegeneration.

Dahun Seo, Anh N Do, Gyujin Heo, Jiseon Kwon, Soomin Song, Catherine Apio, Cheolmin Matthew Lee, Jigyasha Timsina, Katherine Gong, Yike Chen and 13 more

Abstract read
In one paragraph

Article in Nature aging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Engulfment by brain macrophages in a short-lived vertebrate.bioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Dahun Seo *NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0009-0002-6453-1866
Anh N Do *NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.
Gyujin HeoNeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-3499-2848
Jiseon KwonNeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.
Soomin SongNeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0009-0003-3201-6031
Catherine ApioNeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.
Cheolmin Matthew LeeNeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.
Jigyasha TimsinaNeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-4794-9187
Katherine GongNeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0009-0008-7614-9545
Yike ChenNeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0009-0003-9181-8608
Menghan LiuNeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0009-0008-9902-5983
Pat KohlfeldNeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.
John BuddeNeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-7778-7276
Merce BoadaAce Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.
Adelina OrellanaAce Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.
Maria Victoria FernandezAce Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.
Agustin RuizAce Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.
John C MorrisThe Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.
Suzanne E SchindlerThe Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-1680-1465
Laura IbanezNeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.
Taesung ParkDepartment of Statistics, Seoul National University, Seoul, Korea.
Carlos CruchagaNeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-0276-2899
Yun Ju SungNeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA. yunju@wustl.edu.ORCID http://orcid.org/0000-0002-8021-4070

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5M
The natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 2005 to 2025
$49.5M
Research Education ComponentP30AG066444 · NIA · WASHINGTON UNIVERSITY · PI Susan Lynn Stark · 2020 to 2026
$28.7M
USING QUANTITATIVE TRAITS TO IDENTIFY NOVEL GENES FOR ALZHEIMERS DISEASE AND OTHER COMPLEX TRAITSRF1AG053303 · NIA · WASHINGTON UNIVERSITY · PI CLIMER, SHARLEE, CRUCHAGA, CARLOS · 2016 to 2020
$4.0M
GENETIC MODIFIERS OF CEREBROSPINAL FLUID TREM2 IN ALZHEIMER'S DISEASERF1AG058501 · NIA · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS, PICCIO, LAURA · 2018 to 2018
$3.5M
The Familial Alzheimer Sequencing (FASe) ProjectU01AG058922 · NIA · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS, GOATE, ALISON M · 2018 to 2022
$3.5M
IDENTIFYING RARE VARIANTS THAT INCREASE RISK FOR ALZHEIMER'S DISEASER01AG044546 · NIA · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS · 2013 to 2017
$2.7M
Sex-specific Molecular Profiling to Understand Pathology and Identify Causal Genes and Drug Targets forAlzheimer's DiseaseR01AG074007 · NIA · WASHINGTON UNIVERSITY · PI YunJu Sung · 2024 to 2026
$2.4M
National Research Foundation of Korea (NRF) NRF-2022R1A2C1092497NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P30 AG066444NIA NIH HHS R01 AG044546NIA NIH HHS R01 AG074007NIA NIH HHS RF1 AG053303NIA NIH HHS RF1 AG058501NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG058922
6 · The paper itself

Abstract

Age and APOE ε4 are major risk factors for Alzheimer's disease (AD), while sex differences exist in disease prevalence and progression. Cerebrospinal fluid (CSF) proteomics can provide additional insights into brain aging and AD. To examine proteomic changes due to age, sex and apolipoprotein E (APOE) ε4 along with amyloid status before clinical AD occurs, we profiled 6,175 proteins in the CSF from 994 cognitively normal individuals aged 43-91 years. We identified and replicated 2,172 age-associated, 711 sex-associated, 193 APOE ε4-associated and 1,807 amyloid-associated proteins, with extensive overlap suggesting their interplay. These CSF-specific signatures were distinct from those in plasma. Network analysis revealed two proteomic modules-M2 (age-associated, sex-associated and amyloid-associated) and M6 (age-associated and sex-associated)-which were linked to neuropsychiatric and aging-related diseases. Together, our study provides proteomic changes during the early phase of AD, which may help identify new therapeutic targets of AD.

Indexed as

AgingAlzheimer DiseaseCognitionProteomicsAdultAgedAged, 80 and overAge FactorsApolipoprotein E4BiomarkersFemaleHumansMaleMiddle AgedSex FactorsApolipoprotein E4Biomarkers

Identifiers

PMID41087722
PMCPMC12763608

What OpenQuestion 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 OpenQuestion graph.