Evidence map›Paper›PMID 41760935›Full record

ArticleNature aging2026

Structural signature of plasma proteins classifies the status of Alzheimer's disease.

Ahrum Son, Hyunsoo Kim, Jolene K Diedrich, Casimir Bamberger, Heather M Wilkins, Jeffrey M Burns, Jill K Morris, Robert A Rissman, Russell H Swerdlow, John R Yates

Registry-linked trialAbstract read
In one paragraph

Article in Nature aging, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07516119 (Assessing Tools That Predict and Stage Mild Cognitive Impairment), 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.

NCT07516119 recruitingnot on this map

Assessing Tools That Predict and Stage Mild Cognitive Impairment

TypeobservationalSponsorPrevention Research Consortium Corp.Ran2026 to 2029Enrolled100ConditionsMild Cognitive Impairment (MCI), Alzheimer Dementia (AD), Alzheimer Disease (AD), APOE-4 Positive
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

10 authors.

Ahrum SonDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-2706-1340
Hyunsoo KimDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Jolene K DiedrichDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Casimir BambergerDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-3830-4486
Heather M WilkinsUniversity of Kansas Alzheimer's Disease Research Center, University of Kansas Medical Center, Kansas City, KS, USA.ORCID http://orcid.org/0000-0003-4563-4544
Jeffrey M BurnsUniversity of Kansas Alzheimer's Disease Research Center, University of Kansas Medical Center, Kansas City, KS, USA.ORCID http://orcid.org/0000-0001-7609-8954
Jill K MorrisUniversity of Kansas Alzheimer's Disease Research Center, University of Kansas Medical Center, Kansas City, KS, USA.
Robert A RissmanDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
Russell H SwerdlowUniversity of Kansas Alzheimer's Disease Research Center, University of Kansas Medical Center, Kansas City, KS, USA.ORCID http://orcid.org/0000-0003-2948-7230
John R YatesDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA. jyates@scripps.edu.ORCID http://orcid.org/0000-0001-5267-1672

Funding

USCADRC Diversity Supplement PachicanoP30AG066530 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HELENA Chang CHUI, ARTHUR W TOGA · 2020 to 2026
$27.8M
University of Kansas Alzheimer's Disease Research Center (KU ADRC)P30AG072973 · NIA · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Jaime Perales Puchalt · 2021 to 2026
$25.3M
Cell Specific Perturbations of the Proteome in Alzheimer's DiseaseR01AG075862 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI MAXIMOV, ANTON, PETRASCHECK, MICHAEL · 2021 to 2025
$6.6M
Protein conformer-resolved analysis of protein aggregates in Alzheimer's disease with mass spectrometryRF1AG061846 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI YATES III, JOHN R · 2018 to 2019
$3.0M
Contributions of cell type and exosome signaling to prodromal synaptic and circuit changes in Alzheimer's Disease modelsR01AG079517 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI Kristin Kay Baldwin, Michael Petrascheck · 2025 to 2026
$1.7M
3D Proteomics at Single Cell Resolution with Covalent Protein Painting (CPP)R33CA272339 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI John R Yates III · 2024 to 2026
$720k
NCI NIH HHS R33 CA272339NIA NIH HHS P30 AG066530NIA NIH HHS P30 AG072973NIA NIH HHS R01 AG075862NIA NIH HHS R01 AG079517NIA NIH HHS RF1 AG061846U.S. Department of Health & Human Services | National Institutes of Health (NIH) 5R01AG075862U.S. Department of Health & Human Services | National Institutes of Health (NIH) P30-AG066530U.S. Department of Health & Human Services | National Institutes of Health (NIH) P30AG072973U.S. Department of Health & Human Services | National Institutes of Health (NIH) RF1AG061846-01
6 · The paper itself

Abstract

Alzheimer's disease (AD) involves proteostasis dysregulation causing protein misfolding, but whether these structural changes manifest as plasma conformational biomarkers remains unclear. We profiled plasma protein structures from 520 participants including individuals with AD, individuals with mild cognitive impairment (MCI) and healthy controls. Using mass spectrometry and machine learning, we systematically characterized the structural proteome changes associated with ApoE variations and neuropsychiatric symptoms to identify AD-specific signatures. We developed a diagnostic panel using peptides from C1QA, CLUS and ApoB representing AD-associated structural changes. This three-marker panel achieved 83.44% accuracy in three-way classification (healthy versus MCI versus AD). Binary classification yielded area under the receiver operating characteristic curves of 0.9343 for healthy versus MCI and 0.9325 for MCI versus AD. Longitudinal samples were classified with 86.0% accuracy. This multi-marker panel based on plasma protein structural alterations represents a promising diagnostic approach that may enhance early AD detection and provide insights for clinical trials, improving therapeutic outcomes.

Indexed as

Alzheimer DiseaseBlood ProteinsAgedAged, 80 and overApolipoproteins EBiomarkersCognitive DysfunctionFemaleHumansMachine LearningMaleMass SpectrometryProteomeProteomicsApolipoproteins EBiomarkersBlood ProteinsProteome

Identifiers

PMID41760935
PMCPMC13004671

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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.