Evidence map›Paper›PMID 26728181›Full record

ArticleJournal of neuroinflammation2016

Non-alcoholic fatty liver disease induces signs of Alzheimer's disease (AD) in wild-type mice and accelerates pathological signs of AD in an AD model.

Do-Geun Kim, Antje Krenz, Leon E Toussaint, Kirk J Maurer, Sudie-Ann Robinson, Angela Yan, Luisa Torres, Margaret S Bynoe

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed, 3 pooled it
15.8field-weighted citation impact, top 1% of its field
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

115 citing papers in PubMed, 3 syntheses or guidelines pooled it, 337 citations in OpenAlex.

  1. Pooled it
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  4. Article
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  8. Article
  9. Neuroprotective effects ofFrontiers in nutrition · 2026
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  12. Amyloid-beta (1-40) peptide is associated with systemic metabolic health.European journal of clinical investigation · 2026
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  14. International journal of molecular sciences · 2025
    Article
  15. Review
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  17. Review
  18. Article
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  20. Article

55 more citing papers are in PubMed but not listed here.

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

8 authors at 1 institution in 1 country.

Do-Geun KimDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA. dk594@cornell.edu.
Antje KrenzDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA. ak859@cornell.edu.
Leon E ToussaintDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA. let39@cornell.edu.
Kirk J MaurerDepartment of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. km429@cornell.edu.
Sudie-Ann RobinsonDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA. sr687@cornell.edu.
Angela YanDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA. ay296@cornell.edu.
Luisa TorresDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA. lft9@cornell.edu.
Margaret S BynoeDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA. msb76@cornell.edu.
Cornell University · US

Funding

Brain endothelial cell function under adenosine receptor signaling directiveR01NS078018 · NINDS · CORNELL UNIVERSITY · PI BYNOE, MARGARET S. · 2012 to 2016
$2.0M
CD-73 adenosine signaling in the central nervous system in disease and healthR01NS063011 · NINDS · CORNELL UNIVERSITY · PI BYNOE, MARGARET S. · 2008 to 2012
$1.8M
NINDS NIH HHS R01 NS063011NINDS NIH HHS R01 NS078018
6 · The paper itself

Abstract

backgroundNon-alcoholic fatty liver disease (NAFLD) is a chronic liver disease afflicting about one third of the world's population and 30 % of the US population. It is induced by consumption of high-lipid diets and is characterized by liver inflammation and subsequent liver pathology. Obesity and consumption of a high-fat diet are known to increase the risk of Alzheimer's disease (AD). Here, we investigated NAFLD-induced liver inflammation in the pathogenesis of AD.

methodsWT and APP-Tg mice were fed with a standard diet (SD) or a high-fat diet (HFD) for 2, 5 months, or 1 year to induce NAFLD. Another set of APP-Tg mice were removed from HFD after 2 months and put back on SD for 3 months.

resultsDuring acute phase NAFLD, WT and APP-Tg mice developed significant liver inflammation and pathology that coincided with increased numbers of activated microglial cells in the brain, increased inflammatory cytokine profile, and increased expression of toll-like receptors. Chronic NAFLD induced advanced pathological signs of AD in both WT and APP-Tg mice, and also induced neuronal apoptosis. We observed decreased brain expression of low-density lipoprotein receptor-related protein-1 (LRP-1) which is involved in β-amyloid clearance, in both WT and APP-Tg mice after ongoing administration of the HFD. LRP-1 expression correlated with advanced signs of AD over the course of chronic NAFLD. Removal of mice from HFD during acute NAFLD reversed liver pathology, decreased signs of activated microglial cells and neuro-inflammation, and decreased β-amyloid plaque load.

conclusionsOur findings indicate that chronic inflammation induced outside the brain is sufficient to induce neurodegeneration in the absence of genetic predisposition.

Indexed as

Age FactorsAlzheimer DiseaseAmyloid beta-Protein PrecursorAnimalsApolipoproteins ECalcium-Binding ProteinsCytokinesDiet, High-FatDisease Models, AnimalFatsGene Expression RegulationHumansLow Density Lipoprotein Receptor-Related Protein-1MiceMice, TransgenicMicrofilament ProteinsAif1 protein, mouseAmyloid beta-Protein PrecursorApolipoproteins ECalcium-Binding ProteinsCytokinesFatsLow Density Lipoprotein Receptor-Related Protein-1Lrp1 protein, mouseMicrofilament ProteinsNerve Tissue ProteinsReceptors, LDLToll-Like ReceptorsTumor Suppressor Proteins

Identifiers

PMID26728181
PMCPMC4700622
OpenAlexW2223511468

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.