Evidence map›Paper›PMID 42592812›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026

Proteomic signatures of protected APOE ε4 carriers reveal causal pathways associated with delayed Alzheimer's disease onset.

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

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 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 GuenDepartment of Medicine, Quantitative Sciences Unit, Division of Computational Medicine, Stanford University, Stanford, California, USA.ORCID https://orcid.org/0000-0001-6649-8364
Junyoung ParkDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, California, USA.
Andrés Peña-TauberDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, California, USA.
Michael D GreiciusDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, California, USA.

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
The Stanford Extreme Phenotypes in Alzheimer's Disease (StEP AD) CohortR01AG060747 · NIA · STANFORD UNIVERSITY · PI GREICIUS, MICHAEL D · 2018 to 2022
$3.4M
National Institute of HealthNIA NIH HHS AG066515NIA NIH HHS AG072290NIA NIH HHS P30 AG066515NIA NIH HHS R01 AG060747NIA NIH HHS R35 AG072290
6 · The paper itself

Abstract

introductionAPOE ε4 is the strongest common genetic risk factor for Alzheimer's disease (AD), yet many carriers remain cognitively unimpaired into late life. We tested whether protected ε4-first plasma proteomics could identify proteins associated with delayed clinical onset.

methodsWe analyzed harmonized Global Neurodegeneration Proteomics Consortium (GNPC) plasma proteomics. Protected ε4 carriers (ε3/ε4 ≥75 years; ε4/ε4 ≥65 years; Clinical Dementia Rating [CDR] score = 0; n = 456) were compared with ε4 carriers with AD (n = 1096). Protein-wise models adjusted for age, sex, ε4 dosage, and plasma proteomic principal components. Top signals were integrated with loss-of-function burden testing and plasma/cerebrospinal fluid Mendelian randomization.

resultsProtected ε4 status was associated with 721 protein measures. Integrated analyses prioritized LILRA5, DBI, BPNT1, PTEN, EPHA1, and PCDH10 as ε4-modified candidates and OMG, SELENOW, VAT1, and TPPP3 as broader AD-related signals. TREM2 and ACE were also identified. DISCUSSION: This strategy highlights immune, synaptic, metabolic-stress, and myelin/axonal pathways that may delay AD onset.

Indexed as

Alzheimer DiseaseApolipoprotein E4ProteomicsAgedAge of OnsetBiomarkersFemaleHeterozygoteHumansMaleApolipoprotein E4BiomarkersAlzheimer's diseaseAPOE ε4biomarker discoverydelayed disease onsetGlobal Neurodegeneration Proteomics Consortiumloss‐of‐function burdenMendelian randomizationplasma proteomicsresiliencetarget prioritization

Identifiers

PMID42592812
PMCPMC13470879

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.