Evidence map›Paper›PMID 42337953›Full record

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

HDL-mimetic peptide treatment reverses APOE4-induced transcriptomic and lipidomic alterations in the brain of humanized APOE mice.

Allison Chang, Minwoo Kim, Matthew Glittenberg, Wenhui Qu, Danni Li, Ling Li

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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

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

6 authors.

Allison ChangGraduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota, USA.
Minwoo KimDepartment of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA.
Matthew GlittenbergDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
Wenhui QuGraduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota, USA.
Danni LiGraduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota, USA.
Ling LiGraduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota, USA.ORCID https://orcid.org/0000-0002-9245-7387

Funding

Training Grant: Functional Proteomics of AgingT32AG029796 · NIA · UNIVERSITY OF MINNESOTA · PI EDGAR A ARRIAGA, Douglas G Mashek · 2008 to 2026
$6.6M
College of Pharmacy, University of MinnesotaNIH HHS AG056976NIH HHS AG058081NIH HHS AG059654NIH HHS AG077772NIH HHS AG081426NIH training grant T32AG029796
6 · The paper itself

Abstract

introductionThe apolipoprotein E4 (APOE4) allele is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). ApoE4 has reduced lipidation capacity and impaired lipid transport, disrupting neuronal maintenance. The high-density lipoprotein (HDL)-mimetic peptide 4F offers a potential therapeutic strategy.

methodsTo investigate how APOE4 alters brain gene expression and lipid metabolism and to evaluate the therapeutic potential of 4F, we performed dual-omics analysis in APOE4/4 and APOE3/3 mice treated intraperitoneally with D-enantiomer of 4F (D4F) or vehicle for 12 weeks from 10 to 13 months of age.

resultsAPOE4/4 mice showed widespread transcriptomic and lipidomic alterations, including downregulation of lipid metabolism and synaptic pathways, increased ceramides, sphingomyelins, and cholesteryl esters, with decreased diglycerides and triglycerides. D4F treatment shifted relevant gene expression and lipid profiles toward APOE3/3 levels. DISCUSSION: These findings reveal molecular mechanisms underlying APOE4-driven dysregulation and support the therapeutic potential of HDL-mimetic peptides to mitigate APOE4-associated alterations in AD.

Indexed as

Apolipoprotein E4BrainLipid MetabolismLipoproteins, HDLPeptidesTranscriptomeAlzheimer DiseaseAnimalsApolipoprotein A-IApolipoproteins EDisease Models, AnimalHumansLipidomicsMiceMice, TransgenicApolipoprotein A-IApolipoprotein E4Apolipoproteins ED-4F peptideLipoproteins, HDLPeptidesAlzheimer's diseaseAPOEbrainHDL‐mimetic peptidelipidomicstranscriptomics

Identifiers

PMID42337953
PMCPMC13290654

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.