CoChat
Sign Up
Cited by 1Tryptophan and brain disordersAdipokines, Inflammation, and Metabolic DiseasesPharmacogenetics and Drug Metabolism

APOE polymorphism is associated with changes in the kynurenine pathway

Open access
Farup, Per G., Rootwelt, Helge, Hestad, Knut·2023·Genes
DOI 10.3390/genes14101955PMC PMC10606170
Open this paper in CoChat — free accountOpen PDF

Abstract

Background: APOE polymorphism and the Kynurenine pathway (KP) are associated with many disorders, but little is known about associations between APOE polymorphism and the KP. This study explored the associations between the KP and APOE polymorphism in disorders associated with APOE polymorphism and changes in the KP. Methods: Subjects with morbid obesity before and after bariatric surgery (numbers 139 and 95, respectively), depression (number 49), and unspecified neurological symptoms (number 39) were included. The following grouping of the APOE genotypes was used: E2 = ɛ2ɛ2 + ɛ2ɛ3, E3 = ɛ3ɛ3 + ɛ2ɛ4, and E4 = ɛ3ɛ4 + ɛ4ɛ4. The KP metabolites Tryptophan, Kynurenine, Kynurenic acid, Quinolinic acid, and Xanthurenic acid were quantified in serum. Results: The main findings were a significant positive association between E3 and Quinolinic acid (difference between E3 and E2E4: 12.0 (3.5; 18.6) ng/mL); p = 0.005), and a negative association between E4 and Kynurenine (difference between E4 and E2E3: −31.3 (−54.2; −3.2) ng/mL; p = 0.008). Quinolinic acid has been ascribed neurotoxic and inflammatory effects, and Kynurenine is a marker of inflammation. Conclusions: The findings indicate that APOE polymorphism might cause changes in the KP that contribute to the disease. Inflammation could be the link between APOE and the KP.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3390/genes14101955

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Increases in 3- and 4-hydroxyphenylacetic acid in 4s2M are consistent with alterations in aromatic amino acid-related metabolic flux; such metabolites can arise from tyrosine and monoamine pathways and may reflect systemic metabolic influences rather than direct energetic pathway remodeling.

    “In contrast, increases in 3- and 4-hydroxyphenylacetic acid in 4s2M are consistent with alterations in aromatic amino acid–related metabolic flux; such metabolites can arise from tyrosine and monoamine pathways and may reflect systemic metabolic influences rather than direct energetic pathway remodeling”

    From Older adult APOE4 mice exhibit modest immunometabolic adaptation following microglial APOE2 replacement (2027) · cites this paper as Farup et al., 2023

    Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 30

  1. [1]Hubkova B. Valko-Rokytovska M. Cizmarova B. Zabavnikova M. Marekova M. Birkova A. Tryptophan: Its Metabolism along the Kynurenine, Serotonin, and Indole Pathway in Malignant Melanoma Int. J. Mol. Sci. 2022 23 9160 10.3390/ijms23169160 36012419 PMC9408957 · DOI
  2. [2]Marszalek-Grabska M. Walczak K. Gawel K. Wicha-Komsta K. Wnorowska S. Wnorowski A. Turski W.A. Kynurenine emerges from the shadows—Current knowledge on its fate and function Pharmacol. Ther. 2021 225 107845 10.1016/j.pharmthera.2021.107845 33831481 · DOI
  3. [3]Liu J.J. Movassat J. Portha B. Emerging role for kynurenines in metabolic pathologies Curr. Opin. Clin. Nutr. Metab. Care 2019 22 82 90 10.1097/MCO.0000000000000529 30407222 · DOI
  4. [4]Savitz J. The kynurenine pathway: A finger in every pie Mol. Psychiatry 2020 25 131 147 10.1038/s41380-019-0414-4 30980044 PMC6790159 · DOI
  5. [5]Cussotto S. Delgado I. Anesi A. Dexpert S. Aubert A. Beau C. Forestier D. Ledaguenel P. Magne E. Mattivi F. Tryptophan Metabolic Pathways Are Altered in Obesity and Are Associated With Systemic Inflammation Front. Immunol. 2020 11 557 10.3389/fimmu.2020.00557 32351500 PMC7174689 · DOI
  6. [6]Kiluk M. Lewkowicz J. Pawlak D. Tankiewicz-Kwedlo A. Crosstalk between Tryptophan Metabolism via Kynurenine Pathway and Carbohydrate Metabolism in the Context of Cardio-Metabolic Risk-Review J. Clin. Med. 2021 10 2484 10.3390/jcm10112484 34199713 PMC8199979 · DOI
  7. [7]Favennec M. Hennart B. Caiazzo R. Leloire A. Yengo L. Verbanck M. Arredouani A. Marre M. Pigeyre M. Bessede A. The kynurenine pathway is activated in human obesity and shifted toward kynurenine monooxygenase activation Obesity (Silver Spring) 2015 23 2066 2074 10.1002/oby.21199 26347385 · DOI
  8. [8]Marx W. McGuinness A.J. Rocks T. Ruusunen A. Cleminson J. Walker A.J. Gomes-da-Costa S. Lane M. Sanches M. Diaz A.P. The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: A meta-analysis of 101 studies Mol. Psychiatry 2021 26 4158 4178 10.1038/s41380-020-00951-9 33230205 · DOI
  9. [9]Ogyu K. Kubo K. Noda Y. Iwata Y. Tsugawa S. Omura Y. Wada M. Tarumi R. Plitman E. Moriguchi S. Kynurenine pathway in depression: A systematic review and meta-analysis Neurosci. Biobehav. Rev. 2018 90 16 25 10.1016/j.neubiorev.2018.03.023 29608993 · DOI · Paper page
  10. [10]Pu J. Liu Y. Zhang H. Tian L. Gui S. Yu Y. Chen X. Chen Y. Yang L. Ran Y. An integrated meta-analysis of peripheral blood metabolites and biological functions in major depressive disorder Mol. Psychiatry 2021 26 4265 4276 10.1038/s41380-020-0645-4 31959849 PMC8550972 · DOI
  11. [11]Kim Y.K. Jeon S.W. Neuroinflammation and the Immune-Kynurenine Pathway in Anxiety Disorders Curr. Neuropharmacol. 2018 16 574 582 10.2174/1570159X15666170913110426 28901278 PMC5997870 · DOI
  12. [12]Modoux M. Rolhion N. Mani S. Sokol H. Tryptophan Metabolism as a Pharmacological Target Trends Pharmacol. Sci. 2021 42 60 73 10.1016/j.tips.2020.11.006 33256987 · DOI
  13. [14]Khalil Y.A. Rabes J.P. Boileau C. Varret M. APOE gene variants in primary dyslipidemia Atherosclerosis 2021 328 11 22 10.1016/j.atherosclerosis.2021.05.007 34058468 · DOI · Paper page
  14. [15]Chatterjee P. Goozee K. Lim C.K. James I. Shen K. Jacobs K.R. Sohrabi H.R. Shah T. Asih P.R. Dave P. Alterations in serum kynurenine pathway metabolites in individuals with high neocortical amyloid-beta load: A pilot study Sci. Rep. 2018 8 8008 10.1038/s41598-018-25968-7 29789640 PMC5964182 · DOI
  15. [16]van der Velpen V. Teav T. Gallart-Ayala H. Mehl F. Konz I. Clark C. Oikonomidi A. Peyratout G. Henry H. Delorenzi M. Systemic and central nervous system metabolic alterations in Alzheimer’s disease Alzheimers Res. Ther. 2019 11 93 10.1186/s13195-019-0551-7 31779690 PMC6883620 · DOI
  16. [17]Ervik A.O. Solvang S.H. Nordrehaug J.E. Ueland P.M. Midttun O. Hildre A. McCann A. Nygard O. Aarsland D. Giil L.M. The Associations Between Cognitive Prognosis and Kynurenines Are Modified by the Apolipoprotein epsilon4 Allele Variant in Patients With Dementia Int. J. Tryptophan Res. 2019 12 1178646919885637 10.1177/1178646919885637 31798303 PMC6859685 · DOI
  17. [18]Hartai Z. Juhasz A. Rimanoczy A. Janaky T. Donko T. Dux L. Penke B. Toth G.K. Janka Z. Kalman J. Decreased serum and red blood cell kynurenic acid levels in Alzheimer’s disease Neurochem. Int. 2007 50 308 313 10.1016/j.neuint.2006.08.012 17023091 · DOI
  18. [19]Farup P.G. Are the Results of a Combined Behavioural and Surgical Treatment of Morbid Obesity Satisfactory and Predictable? Nutrients 2020 12 1997 10.3390/nu12071997 32635628 PMC7400840 · DOI
  19. [21]Farup P.G. Hamarsland H. Molmen K.S. Ellefsen S. Hestad K. The Kynurenine Pathway in Healthy Subjects and Subjects with Obesity, Depression and Chronic Obstructive Pulmonary Disease Pharmaceuticals 2023 16 351 10.3390/ph16030351 36986451 PMC10053928 · DOI
  20. [22]Hestad K.A. Engedal K. Whist J.E. Farup P.G. The Relationships among Tryptophan, Kynurenine, Indoleamine 2,3-Dioxygenase, Depression, and Neuropsychological Performance Front. Psychol. 2017 8 1561 10.3389/fpsyg.2017.01561 29046648 PMC5632654 · DOI
  21. [23]Han S. Xu Y. Gao M. Wang Y. Wang J. Liu Y. Wang M. Zhang X. Serum apolipoprotein E concentration and polymorphism influence serum lipid levels in Chinese Shandong Han population Medicine 2016 95 e5639 10.1097/MD.0000000000005639 27977609 PMC5268055 · DOI
  22. [24]Sorgdrager F.J.H. Vermeiren Y. Van Faassen M. van der Ley C. Nollen E.A.A. Kema I.P. De Deyn P.P. Age- and disease-specific changes of the kynurenine pathway in Parkinson’s and Alzheimer’s disease J. Neurochem. 2019 151 656 668 10.1111/jnc.14843 31376341 PMC6899862 · DOI
  23. [25]Lugo-Huitron R. Ugalde Muniz P. Pineda B. Pedraza-Chaverri J. Rios C. Perez-de la Cruz V. Quinolinic acid: An endogenous neurotoxin with multiple targets Oxid. Med. Cell Longev. 2013 2013 104024 10.1155/2013/104024 24089628 PMC3780648 · DOI · Paper page
  24. [26]Bansal Y. Singh R. Parhar I. Kuhad A. Soga T. Quinolinic Acid and Nuclear Factor Erythroid 2-Related Factor 2 in Depression: Role in Neuroprogression Front. Pharmacol. 2019 10 452 10.3389/fphar.2019.00452 31164818 PMC6536572 · DOI
  25. [27]Watne L.O. Pollmann C.T. Neerland B.E. Quist-Paulsen E. Halaas N.B. Idland A.V. Hassel B. Henjum K. Knapskog A.B. Frihagen F. Cerebrospinal fluid quinolinic acid is strongly associated with delirium and mortality in hip-fracture patients J. Clin. Investig. 2023 133 e163472 10.1172/JCI163472 36409557 PMC9843060 · DOI
  26. [28]Phing A.H. Makpol S. Nasaruddin M.L. Wan Zaidi W.A. Ahmad N.S. Embong H. Altered Tryptophan-Kynurenine Pathway in Delirium: A Review of the Current Literature Int. J. Mol. Sci. 2023 24 5580 10.3390/ijms24065580 36982655 PMC10056900 · DOI
  27. [29]Alexander D.M. Williams L.M. Gatt J.M. Dobson-Stone C. Kuan S.A. Todd E.G. Schofield P.R. Cooper N.J. Gordon E. The contribution of apolipoprotein E alleles on cognitive performance and dynamic neural activity over six decades Biol. Psychol. 2007 75 229 238 10.1016/j.biopsycho.2007.03.001 17433528 · DOI
  28. [30]Zokaei N. Giehl K. Sillence A. Neville M.J. Karpe F. Nobre A.C. Husain M. Sex and APOE: A memory advantage in male APOE epsilon4 carriers in midlife Cortex 2017 88 98 105 10.1016/j.cortex.2016.12.016 28086184 PMC5333781 · DOI
  29. [31]Jochemsen H.M. Muller M. van der Graaf Y. Geerlings M.I. APOE epsilon4 differentially influences change in memory performance depending on age. The SMART-MR study Neurobiol. Aging 2012 33 832.e15 832.e22 10.1016/j.neurobiolaging.2011.07.016 21908077 · DOI
  30. [32]Kuo C.L. Pilling L.C. Atkins J.L. Kuchel G.A. Melzer D. ApoE e2 and aging-related outcomes in 379,000 UK Biobank participants Aging 2020 12 12222 12233 10.18632/aging.103405 32511104 PMC7343499 · DOI · Paper page

Cited by

Sorted by citations

Authors
Farup, P. G., Rootwelt, H., & Hestad, K.
Affiliations
  • Norwegian University of Science and Technology (NO)
  • Oslo University Hospital (NO)
Corresponding author
Farup, Per G.
ORCID
Venue
Genes
Publisher
MDPI AG
Published
2023-10-18
Volume
14
Issue
10
Pages
1955
ISSN
2073-4425 (ISSN-L)
DOI
10.3390/genes14101955
PMC
PMC10606170
OpenAlex
W4387744237
Cited by
1
References
2
Citations by year
2026: 1
FWCI
0.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Genes (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
Funders
Innlandet Hospital Trust, Brumunddal, Norway and Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
Topics
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords
APOE polymorphism, kynurenine pathway, quinolinic acid, kynurenine, kynurenic acid, xanthurenic acid, tryptophan metabolism, obesity, bariatric surgery, depression, inflammation, neuroinflammation, APOE ε4
MeSH terms
Apolipoproteins E, Humans, Inflammation, Kynurenine, Tryptophan, Quinolinic Acid

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review