Evidence map›Paper›PMID 38713704›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024

Assessment of neurovascular uncoupling: APOE status is a key driver of early metabolic and vascular dysfunction.

Kristen D Onos, Peter B Lin, Ravi S Pandey, Scott A Persohn, Charles P Burton, Ethan W Miner, Kierra Eldridge, Jonathan Nyandu Kanyinda, Kate E Foley, Gregory W Carter and 2 more

Abstract read
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
–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

13 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Low frequency BOLD oscillations,medRxiv : the preprint server for health sciences · 2025
    Article
  9. Neurometabolic and vascular dysfunction as an early diagnostic for Alzheimer's disease and related dementias.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  10. Article
  11. WSB.bioRxiv : the preprint server for biology · 2025
    Article
  12. Assessment of neurovascular uncoupling: APOE status is a key driver of early metabolic and vascular dysfunction.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  13. Three major effects of APOEFrontiers in aging neuroscience · 2024
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Kristen D OnosThe Jackson Laboratory, Bar Harbor, Maine, USA.
Peter B LinStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Ravi S PandeyThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.
Scott A PersohnStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Charles P BurtonStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Ethan W MinerStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Kierra EldridgeStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Jonathan Nyandu KanyindaThe Jackson Laboratory, Bar Harbor, Maine, USA.
Kate E FoleyThe Jackson Laboratory, Bar Harbor, Maine, USA.
Gregory W CarterThe Jackson Laboratory, Bar Harbor, Maine, USA.
Gareth R HowellThe Jackson Laboratory, Bar Harbor, Maine, USA.
Paul R TerritoStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Funding

The IU/JAX Alzheimer's Disease Precision Models Center: Rat F344U54AG054345 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI Gareth R Howell · 2016 to 2026
$95.6M
UC Irvine MODEL-ADU54AG054349 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Kim Green · 2017 to 2026
$71.9M
TREAT AD Structural Biology CoreU54AG065187 · NIA · EMORY UNIVERSITY · PI Gregory W Carter, ALLAN I LEVEY · 2019 to 2026
$69.7M
Modulation of TNFα as a Treatment for Alzheimer's Disease and Related DementiaR21AG078575 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI HOWELL, GARETH R, TERRITO, PAUL RICHARD · 2022 to 2022
$469k
NIA NIH HHS R21 AG078575NIA NIH HHS U54 AG054345NIA NIH HHS U54 AG054349NIA NIH HHS U54 AG065187NIH/NIA R21-AG078575-01NIH/NIA U54-AG054345NIH/NIA U54-AG054349
6 · The paper itself

Abstract

backgroundAlzheimer's disease (AD) is the most common cause of dementia worldwide, with apolipoprotein Eε4 (APOEε4) being the strongest genetic risk factor. Current clinical diagnostic imaging focuses on amyloid and tau; however, new methods are needed for earlier detection.

methodsPET imaging was used to assess metabolism-perfusion in both sexes of aging C57BL/6J, and hAPOE mice, and were verified by transcriptomics, and immunopathology.

resultsAll hAPOE strains showed AD phenotype progression by 8 months, with females exhibiting the regional changes, which correlated with GO-term enrichments for glucose metabolism, perfusion, and immunity. Uncoupling analysis revealed APOEε4/ε4 exhibited significant Type-1 uncoupling (↓ glucose uptake, ↑ perfusion) at 8 and 12 months, while APOEε3/ε4 demonstrated Type-2 uncoupling (↑ glucose uptake, ↓ perfusion), while immunopathology confirmed cell specific contributions. DISCUSSION: This work highlights APOEε4 status in AD progression manifests as neurovascular uncoupling driven by immunological activation, and may serve as an early diagnostic biomarker. HIGHLIGHTS: We developed a novel analytical method to analyze PET imaging of

Indexed as

Apolipoprotein E4Apolipoproteins ENeurovascular CouplingPositron-Emission TomographyAlzheimer DiseaseAnimalsBrainDisease Models, AnimalDisease ProgressionFemaleGlucoseMaleMiceMice, Inbred C57BLMice, TransgenicApolipoprotein E4Apolipoproteins EGlucoseAlzheimer's diseaseAPOEmetabolismperfusionuncoupling

Identifiers

PMID38713704
PMCPMC11247674

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.