Evidence map›Paper›PMID 42094129›Full record

ArticlemedRxiv : the preprint server for health sciences2026

Proteomic Signatures of Protected

Yann Le Guen, Junyoung Park, Andrés Peña-Tauber, Michael D Greicius

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the 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.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Yann Le GuenQuantitative Sciences Unit, Division of Computational Medicine, Department of Medicine Stanford University, Stanford, CA.
Junyoung ParkDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA.
Andrés Peña-TauberDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA.
Michael D GreiciusDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA.

Funding

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
Illuminating the APOE Locus with Long-Read Sequencing and Targeted GenomicsR35AG072290 · NIA · STANFORD UNIVERSITY · PI GREICIUS, MICHAEL D · 2021 to 2025
$4.6M
NIA NIH HHS P30 AG066515NIA NIH HHS R35 AG072290
6 · The paper itself

Abstract

introduction

methodsWe analyzed harmonized plasma proteomics from the Global Neurodegeneration Proteomics Consortium. Protected ε4 carriers (ε3/ε4 aged ≥75 years; ε4/ε4 aged ≥65 years; CDR=0; n=456) were compared with ε4 carriers with AD (n=1,096). Protein-wise linear models adjusted for age, sex, ε4 dosage, and plasma proteomic principal components. Top signals were integrated with high-confidence loss-of-function burden testing and plasma/CSF Mendelian randomization.

resultsε4 protected was associated with 721 protein levels. Integrated analyses prioritized proteins linked to ε4-modified disease biology, including LILRA5, DBI, BPNT1, PTEN, EPHA1, and PCDH10, and proteins aligned with broader AD-related change, including OMG, SELENOW, VAT1, and TPPP3. TREM2 and ACE were also identified, providing internal biological validation of the approach. DISCUSSION: A protected-ε4-first plasma proteomic strategy highlights immune, synaptic, metabolic-stress, and myelin/axonal pathways that may delay AD onset and helps prioritize candidate ε4-specific modifiers for prevention-focused therapeutics.

Identifiers

PMID42094129
PMCPMC13142821

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.