Evidence map›Paper›PMID 42860522›Full record

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

ApoE lipidation state directs immunometabolic reprogramming of human microglia.

Tsion G Shiferaw, Snigdha Sarkar, Katelyn M Baker, Rowan S Wooldridge, Hannah M Binfet, Victoria N Prozapas, Chinemerem P Ogbu, Athena A Schepmoes, Isaac K Attah, Christy S Niemeyer and 5 more

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

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

15 authors.

Tsion G ShiferawDivision of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.ORCID https://orcid.org/0009-0005-9617-8536
Snigdha SarkarBiological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington, USA.
Katelyn M BakerDivision of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Rowan S WooldridgeBiological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington, USA.
Hannah M BinfetBiological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington, USA.
Victoria N ProzapasBiological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington, USA.
Chinemerem P OgbuBiological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington, USA.
Athena A SchepmoesBiological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington, USA.
Isaac K AttahBiological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington, USA.
Christy S NiemeyerDepartment of Neurology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.ORCID https://orcid.org/0000-0001-6830-6522
Kayla G SprengerDepartment of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, Colorado, USA.ORCID https://orcid.org/0000-0002-7505-7920
James E HassellDivision of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.ORCID https://orcid.org/0000-0002-8336-4875
Robert H EckelDivision of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.ORCID https://orcid.org/0000-0002-4870-4600
John T MelchiorBiological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington, USA.ORCID https://orcid.org/0000-0003-3781-2566
Kimberley D BruceDivision of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.ORCID https://orcid.org/0000-0001-5656-1534

Funding

University of Colorado Anschutz Medical Campus DRCP30DK116073 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI LORI SUSSEL · 2020 to 2026
$10.8M
ZEBRAFISH TRANSGENIC CORE - ROCKY MOUNTAIN NEUROLOGICAL DISORDERS CORE CENTERP30NS048154 · NINDS · UNIVERSITY OF COLORADO DENVER · PI RIBERA, ANGELES BADELL · 2004 to 2020
$10.1M
Targeting Microglial Lipoprotein Lipase in Alzheimer's diseaseR01AG079217 · NIA · UNIVERSITY OF COLORADO DENVER · PI Kimberley D Bruce · 2022 to 2026
$3.0M
The impact of brain lipoprotein structure and composition on amyloid beta metabolism and Alzheimer's diseaseR01NS125591 · NINDS · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI John Melchior · 2024 to 2026
$2.2M
Research Training Program in Metabolism, Obesity and Type 2 DiabetesT32DK120521 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI DANIEL Holland BESSESEN · 2020 to 2026
$2.1M
NIA NIH HHS R01 AG079217NIDDK NIH HHS P30 DK116073NIDDK NIH HHS T32 DK120521NIH HHS R01AG079217-01NINDS NIH HHS P30 NS048154NINDS NIH HHS R01 NS125591NINDS NIH HHS R01NS125591Strategic Infrastructure for Research Committee T32 2T32DK120521-06
6 · The paper itself

Abstract

introductionApoE ε4 is the strongest genetic risk factor for Alzheimer's disease (AD). Emerging evidence suggests that ApoE4 increases AD risk by disrupting microglial metabolism and function. However, whether ApoE lipidation state contributes to microglial dysfunction remains poorly understood.

methodsHuman microglia were treated with lipid-free (LF) or lipid-bound ApoE3 or ApoE4. Label-free, live-cell holotomography and global proteomics were used to assess isoform- and lipidation-specific effects on lipid droplet (LD) dynamics, mitochondrial morphology, and microglial phenotype.

resultsApoE4 treatment resulted in fewer but enlarged LDs and increased mitochondrial fragmentation compared to ApoE3, effects that were enhanced by lipid-bound ApoE4. Proteomic analyses revealed a strong type I interferon response in cells exposed to LF-ApoE, which was exacerbated by LF-ApoE4. DISCUSSION: These findings indicate that lipid-bound ApoE4 drives metabolic reprogramming, whereas LF-ApoE4 promotes inflammatory signaling, identifying ApoE lipidation as a critical modifier of ApoE4-associated AD risk.

Indexed as

Apolipoprotein E3Apolipoprotein E4Apolipoproteins ELipid MetabolismMicrogliaAlzheimer DiseaseHumansLipid DropletsMetabolic ReprogrammingMitochondriaApolipoprotein E3Apolipoprotein E4Apolipoproteins EAlzheimer's diseaseAPOE ε4apolipoprotein Eholotomographylipid metabolismmicroglia

Identifiers

PMID42860522
PMCPMC13655218

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.