Evidence map›Paper›PMID 40164724›Full record

ArticleNature medicine2025

A cerebrospinal fluid synaptic protein biomarker for prediction of cognitive resilience versus decline in Alzheimer's disease.

Hamilton Se-Hwee Oh, Deniz Yagmur Urey, Linda Karlsson, Zeyu Zhu, Yuanyuan Shen, Amelia Farinas, Jigyasha Timsina, Michael R Duggan, Jingsha Chen, Ian H Guldner and 28 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing 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

78 citing papers in PubMed.

  1. Trial
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  12. Menopausal insomnia as a modifiable node of dementia risk: Mechanistic insights and intervention strategies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
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18 more citing papers are in PubMed but not listed here.

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

38 authors.

Hamilton Se-Hwee OhGraduate Program in Stem Cell and Regenerative Medicine, Stanford University, Stanford, CA, USA. hamilton.oh@mssm.edu.ORCID http://orcid.org/0000-0001-8192-7593
Deniz Yagmur UreyThe Phil and Penny Knight Initiative for Brain Resilience, Stanford University, Stanford, CA, USA.
Linda KarlssonClinical Memory Research Unit, Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0002-0630-772X
Zeyu ZhuInstitute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.
Yuanyuan ShenDepartment of Psychiatry, Washington University, St. Louis, MO, USA.
Amelia FarinasThe Phil and Penny Knight Initiative for Brain Resilience, Stanford University, Stanford, CA, USA.
Jigyasha TimsinaDepartment of Psychiatry, Washington University, St. Louis, MO, USA.
Michael R DugganLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-1029-4423
Jingsha ChenDepartment of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Ian H GuldnerDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Nader MorshedBoston Children's Hospital, F.M. Kirby Neurobiology Center, Boston, MA, USA.ORCID http://orcid.org/0000-0002-0346-9651
Chengran YangDepartment of Psychiatry, Washington University, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-4577-5590
Daniel WesternDepartment of Psychiatry, Washington University, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-3725-9553
Muhammad AliDepartment of Psychiatry, Washington University, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-1399-6631
Yann Le GuenDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-6649-8364
Alexandra TrelleLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Sanna-Kaisa HerukkaDepartment of Neurology, Kuopio University Hospital and Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland.
Tuomas RauramaaDepartment of Pathology, Kuopio University Hospital and Institute of Clinical Medicine - Pathology, University of Eastern Finland, Kuopio, Finland.
Mikko HiltunenInstitute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
Anssi LipponenInstitute of Biomedicine, University of Eastern Finland, Kuopio, Finland.ORCID http://orcid.org/0000-0002-4403-9084
Antti J LuikkuDepartment of Neurosurgery, Kuopio University Hospital and Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland, Kuopio, Finland.
Kathleen L PostonThe Phil and Penny Knight Initiative for Brain Resilience, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-3424-7143
Elizabeth MorminoDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Anthony D WagnerWu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-0624-4543
Edward N WilsonThe Phil and Penny Knight Initiative for Brain Resilience, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-0640-5247
Divya ChannappaThe Phil and Penny Knight Initiative for Brain Resilience, Stanford University, Stanford, CA, USA.
Ville LeinonenDepartment of Neurosurgery, Kuopio University Hospital and Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland, Kuopio, Finland.
Beth StevensBoston Children's Hospital, F.M. Kirby Neurobiology Center, Boston, MA, USA.
Alexander J EhrenbergMemory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Rebecca F GottesmanStroke Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-9504-1256
Josef CoreshDepartments of Population Health and Medicine, New York University Grossman School of Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-4598-0669
Keenan A WalkerLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-5989-9853
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.ORCID http://orcid.org/0000-0003-3930-4354
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Nicolai FranzmeierInstitute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.ORCID http://orcid.org/0000-0001-9736-2283
Oskar HanssonClinical Memory Research Unit, Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0001-8467-7286
Carlos CruchagaDepartment of Psychiatry, Washington University, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-0276-2899
Tony Wyss-CorayThe Phil and Penny Knight Initiative for Brain Resilience, Stanford University, Stanford, CA, USA. twc@stanford.edu.ORCID http://orcid.org/0000-0001-5893-0831

Funding

National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5M
ARIC Neurocognitive Study (ARIC-NCS) Renewal 2023-2028U01HL096812 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI JOSEF CORESH, THOMAS H MOSLEY · 2010 to 2026
$65.7M
The natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 2005 to 2025
$49.5M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
Stanford Center for Clinical & Translational Education and Research (Spectrum)UL1TR003142 · NCATS · STANFORD UNIVERSITY · PI O'HARA, RUTH M · 2019 to 2023
$45.0M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
Research Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI Corinne Pettigrew · 2020 to 2026
$29.3M
Stanford Alzheimer's Disease Research CenterAdmin Supp: Developing iPSC models for AD and PDP30AG066515 · NIA · STANFORD UNIVERSITY · PI Lisa Goldman Rosas · 2020 to 2026
$29.0M
Research Education ComponentP30AG066444 · NIA · WASHINGTON UNIVERSITY · PI Susan Lynn Stark · 2020 to 2026
$28.7M
Rush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
NCATS NIH HHS UL1 TR003142NHLBI NIH HHS 75N92022D00001NHLBI NIH HHS 75N92022D00002NHLBI NIH HHS 75N92022D00003NHLBI NIH HHS 75N92022D00004NHLBI NIH HHS 75N92022D00005NHLBI NIH HHS U01 HL096812NHLBI NIH HHS U01 HL096814NHLBI NIH HHS U01 HL096899NHLBI NIH HHS U01 HL096902NHLBI NIH HHS U01 HL096917NIA NIH HHS F32 AG079666NIA NIH HHS K99 AG088304NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG066515NIA NIH HHS P30 AG072975NIA NIH HHS P50 AG047366NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG044546NIA NIH HHS R01 AG048076NIA NIH HHS R01 AG072255NIA NIH HHS R01 AG074339NIA NIH HHS R21 AG058859NIA NIH HHS RF1 AG053303NIA NIH HHS RF1 AG058501NIA NIH HHS RF1 AG074007NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG058922NIA NIH HHS U01 AG061356NIA NIH HHS U24 AG021886NIMH NIH HHS T32 MH020016NIMH NIH HHS T32 MH135853U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) AG072255U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) P30AG066515
6 · The paper itself

Abstract

Rates of cognitive decline in Alzheimer's disease (AD) are extremely heterogeneous. Although biomarkers for amyloid-beta (Aβ) and tau proteins, the hallmark AD pathologies, have improved pathology-based diagnosis, they explain only 20-40% of the variance in AD-related cognitive impairment (CI). To discover novel biomarkers of CI in AD, we performed cerebrospinal fluid (CSF) proteomics on 3,397 individuals from six major prospective AD case-control cohorts. Synapse proteins emerged as the strongest correlates of CI, independent of Aβ and tau. Using machine learning, we derived the CSF YWHAG:NPTX2 synapse protein ratio, which explained 27% of the variance in CI beyond CSF pTau

Indexed as

Alzheimer DiseaseBiomarkersCognitive DysfunctionNerve Tissue ProteinsSynapsesAgedAged, 80 and overAmyloid beta-PeptidesCase-Control StudiesCognitionFemaleHumansMaleMiddle AgedProteomicstau ProteinsAmyloid beta-PeptidesBiomarkersNerve Tissue Proteinstau Proteins

Identifiers

PMID40164724
PMCPMC12092275

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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.