CoChat
Sign Up
Cited by 33

The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.

Changes in lipid metabolism track with the progression of neurofibrillary pathology in tauopathies

Olešová, Dominika, Dobešová, Dana, Majerová, Petra, Brumarová, Radana, Kvasnička, Aleš, Kouřil, Štěpán, Stevens, Eva, Hanes, Jozef, Fialová, Ľubica, Michalicová, Alena, Piešťanský, Juraj, Šinský, Jakub, Kaňovský, Petr, Friedecký, David, Kováč, Andrej·2024·Journal of Neuroinflammation
DOI 10.1186/s12974-024-03060-4PMC PMC10976809

Published version of a preprint

Open this paper in CoChat — free account

Abstract

Background: Accumulation of tau leads to neuroinflammation and neuronal cell death in tauopathies, including Alzheimer’s disease. As the disease progresses, there is a decline in brain energy metabolism. However, the role of tau protein in regulating lipid metabolism remains less characterized and poorly understood. Methods: We used a transgenic rat model for tauopathy to reveal metabolic alterations induced by neurofibrillary pathology. Transgenic rats express a tau fragment truncated at the N- and C-terminals. For phenotypic profiling, we performed targeted metabolomic and lipidomic analysis of brain tissue, CSF, and plasma, based on the LC-MS platform. To monitor disease progression, we employed samples from transgenic and control rats aged 4, 6, 8, 10, 12, and 14 months. To study neuron-glia interplay in lipidome changes induced by pathological tau we used well well-established multicomponent cell model system. Univariate and multivariate statistical approaches were used for data evaluation. Results: We showed that tau has an important role in the deregulation of lipid metabolism. In the lipidomic study, pathological tau was associated with higher production of lipids participating in protein fibrillization, membrane reorganization, and inflammation. Interestingly, significant changes have been found in the early stages of tauopathy before the formation of high-molecular-weight tau aggregates and neurofibrillary pathology. Increased secretion of pathological tau protein in vivo and in vitro induced upregulated production of phospholipids and sphingolipids and accumulation of lipid droplets in microglia. We also found that this process depended on the amount of extracellular tau. During the later stages of tauopathy, we found a connection between the transition of tau into an insoluble fraction and changes in brain metabolism. Conclusion: Our results revealed that lipid metabolism is significantly affected during different stages of tau pathology. Thus, our results demonstrate that the dysregulation of lipid composition by pathological tau disrupts the microenvironment, further contributing to the propagation of pathology.

Overview

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 · 10.1186/s12974-024-03060-4

Cites

7 of 7 references verified0 citation errors · 0 not checkable

Statistics

Verification

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?

  • Increased cholesterol levels are present in tandem with neuronal dysfunction and tau aggregation in several experimental models.

    “Using several experimental models, it has been shown that increased cholesterol levels are present in tandem with neuronal dysfunction and tau aggregation4,5,18–25.”

    From GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau (2025) · cites this paper as [24]

Self-check

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

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

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 72

  1. Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL. Alzheimer’s disease. Nat Rev Dis Primers. 2015;1:15056. · DOI · Paper page
  2. Avila J. Tau aggregation into fibrillar polymers: taupathies. FEBS Lett. 2000;476:89–92. · DOI
  3. Cantrelle F-X, Loyens A, Trivelli X, Reimann O, Despres C, Gandhi NS et al. Phosphorylation and O-GlcNAcylation of the PHF-1 epitope of tau protein induce local conformational changes of the C-Terminus and modulate tau self-assembly into Fibrillar aggregates. Front Mol Neurosci. 2021;14. · DOI
  4. Kawarabayashi T. Dimeric amyloid protein rapidly accumulates in lipid rafts followed by Apolipoprotein E and Phosphorylated Tau Accumulation in the Tg2576 mouse model of Alzheimer’s Disease. J Neurosci. 2004;24:3801–9. · DOI · Paper page
  5. Gellermann GP, Appel TR, Davies P, Diekmann S. Paired helical filaments contain small amounts of cholesterol, phosphatidylcholine and sphingolipids. Biol Chem. 2006;387. · DOI
  6. Lee JH, Han J, Woo JH, Jou I. 25-Hydroxycholesterol suppress IFN-γ-induced inflammation in microglia by disrupting lipid raft formation and caveolin-mediated signaling endosomes. Free Radic Biol Med. 2022;179:252–65. · DOI
  7. Song C, Manku MS, Horrobin DF. Long-chain polyunsaturated fatty acids modulate Interleukin-1β–Induced Changes in Behavior, Monoaminergic Neurotransmitters, and brain inflammation in rats. J Nutr. 2008;138:954–63. · DOI
  8. Don AS, Hsiao J-HT, Bleasel JM, Couttas TA, Halliday GM, Kim WS. Altered lipid levels provide evidence for myelin dysfunction in multiple system atrophy. Acta Neuropathol Commun. 2014;2:150. · DOI · Paper page
  9. Bohdanowicz M, Grinstein S. Role of phospholipids in Endocytosis, phagocytosis, and Macropinocytosis. Physiol Rev. 2013;93:69–106. · DOI
  10. Fanni AM, Vander Zanden CM, Majewska PV, Majewski J, Chi EY. Membrane-mediated fibrillation and toxicity of the tau hexapeptide PHF6. J Biol Chem. 2019;294:15304–17. · DOI
  11. Newton AC. Lipid activation of protein kinases. J Lipid Res. 2009;50:S266–71. · DOI
  12. Karunakaran I, Alam S, Jayagopi S, Frohberger SJ, Hansen JN, Kuehlwein J, et al. Neural sphingosine 1-phosphate accumulation activates microglia and links impaired autophagy and inflammation. Glia. 2019;67:1859–72. · DOI
  13. Filipcik P, Zilka N, Bugos O, Kucerak J, Koson P, Novak P et al. First transgenic rat model developing progressive cortical neurofibrillary tangles. Neurobiol Aging [Internet]. 2012;33:1448–56. https://doi.org/10.1016/j.neurobiolaging.2010.10.015. · DOI
  14. Majerova P, Olesova D, Golisova G, Buralova M, Michalicova A, Vegh J et al. Analog of kynurenic acid decreases tau pathology by modulating astrogliosis in rat model for tauopathy. Biomedicine & Pharmacotherapy [Internet]. 2022;152:113257. Available from: http://biorxiv.org/content/early/2022/04/19/2022.04.19.488739.abstract. · DOI
  15. Xuan Q, Hu C, Yu D, Wang L, Zhou Y, Zhao X, et al. Development of a high Coverage Pseudotargeted Lipidomics Method based on Ultra-high Performance Liquid Chromatography–Mass Spectrometry. Anal Chem. 2018;90:7608–16. · DOI
  16. Drotleff B, Roth SR, Henkel K, Calderón C, Schlotterbeck J, Neukamm MA, et al. Lipidomic profiling of non-mineralized dental plaque and biofilm by untargeted UHPLC-QTOF-MS/MS and SWATH acquisition. Anal Bioanal Chem. 2020;412:2303–14. · DOI
  17. Yuan M, Breitkopf SB, Yang X, Asara JM. A positive/negative ion-switching, targeted mass spectrometry-based metabolomics platform for bodily fluids, cells, and fresh and fixed tissue. Nat Protoc. 2012;7:872–81. · DOI
  18. Puris E, Kouřil Š, Najdekr L, Auriola S, Loppi S, Korhonen P, et al. Metabolomic, Lipidomic and Proteomic Characterisation of Lipopolysaccharide-induced inflammation mouse model. Neuroscience. 2022;496:165–78. · DOI
  19. Zilkova M, Zilka N, Kovac A, Kovacech B, Skrabana R, Skrabanova M, et al. Hyperphosphorylated Truncated protein tau induces Caspase-3 independent apoptosis-like Pathway in the Alzheimer’s Disease Cellular Model. J Alzheimer’s Disease. 2011;23:161–9. · DOI
  20. Lee VM-Y, Wang J, Trojanowski JQ. [6] purification of paired helical filament tau and normal tau from human brain tissue. Methods in Enyzmologzy. Academic; 1999. pp. 81–9. · DOI
  21. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a Software Environment for Integrated Models of Biomolecular Interaction Networks. Genome Res. 2003;13:2498–504. · DOI · Paper page
  22. Chong J, Soufan O, Li C, Caraus I, Li S, Bourque G, et al. MetaboAnalyst 4.0: towards more transparent and integrative metabolomics analysis. Nucleic Acids Res. 2018;46:W486–94. · DOI
  23. Molenaar MR, Jeucken A, van de Wassenaar TA, Brouwers JF, Helms JB. LION/web: a web-based ontology enrichment tool for lipidomic data analysis. Gigascience. 2019;8. · DOI
  24. Tumati S, Opmeer EM, Marsman J-BC, Martens S, Reesink FE, De Deyn PP, et al. Lower Choline and Myo-Inositol in Temporo-Parietal cortex is Associated with apathy in Amnestic MCI. Front Aging Neurosci. 2018;10:1–9. · DOI
  25. Huang W, Ph D, Alexander GE, Daly EM, Shetty HU, Krasuski JS, et al. High brain myo-inositol levels in the Predementia phase of Alzheimer ’ s disease in adults with down ’ s syndrome. Am J Psychiatry. 1999;156:1879–86. · DOI
  26. Sajja VSSS, Perrine SA, Ghoddoussi F, Hall CS, Galloway MP, VandeVord PJ. Blast neurotrauma impairs working memory and disrupts prefrontal myo-inositol levels in rats. Molecular and Cellular Neuroscience [Internet]. 2014 [cited 2018 May 13];59:119–26. Available from: https://www.sciencedirect.com/science/article/pii/S1044743114000232?via%3Dihub. · DOI
  27. Aksenov M, Aksenova M, Butterfield DA, Markesbery WR. Oxidative Modification of Creatine Kinase BB in Alzheimer’s Disease Brain. J Neurochem. 2002;74:2520–7. · DOI
  28. Barnes VM, Teles R, Trivedi HM, Devizio W, Xu T, Mitchell MW, et al. Acceleration of Purine Degradation by Periodontal diseases. J Dent Res. 2009;88:851–5. · DOI
  29. Yan X, Hu Y, Wang B, Wang S, Zhang X. Metabolic dysregulation contributes to the progression of Alzheimer’s Disease. Front Neurosci. 2020;14. · DOI
  30. Westergaard N, Sonnewald U, Unsgård G, Peng L, Hertz L, Schousboe A. Uptake, Release, and Metabolism of Citrate in Neurons and Astrocytes in Primary Cultures. J Neurochem [Internet]. 1994;62:1727–33. https://doi.org/10.1046/j.1471-4159.1994.62051727.x. · DOI
  31. Pascente R, Frigerio F, Rizzi M, Porcu L, Boido M, Davids J, et al. Cognitive deficits and brain myo-inositol are early biomarkers of epileptogenesis in a rat model of epilepsy. Neurobiol Dis. 2016;93:146–55. · DOI
  32. Sweeney MD, Sagare AP, Zlokovic BV. Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat Rev Neurol. 2018;14:133–50. · DOI · Paper page
  33. Clarke JR, Ribeiro FC, Frozza RL, De Felice FG, Lourenco MV. Metabolic Dysfunction in Alzheimer’s Disease: From Basic Neurobiology to Clinical Approaches. Perry G, Avila J, Moreira PI, Sorensen AA, Tabaton M, editors. Journal of Alzheimer’s Disease. 2018;64:S405–26. · DOI
  34. Villamil-Ortiz JG, Barrera-Ocampo A, Arias-Londoño JD, Villegas A, Lopera F, Cardona-Gómez GP. Differential Pattern of Phospholipid Profile in the Temporal Cortex from E280A-Familiar and Sporadic Alzheimer’s Disease Brains. Journal of Alzheimer’s Disease [Internet]. 2017;61:209–19. Available from: https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/JAD-170554 · DOI · Paper page
  35. Whiley L, Sen A, Heaton J, Proitsi P, García-Gómez D, Leung R et al. Evidence of altered phosphatidylcholine metabolism in Alzheimer’s disease. Neurobiol Aging [Internet]. 2014 [cited 2020 Feb 7];35:271–8. Available from: https://www.sciencedirect.com/science/article/pii/S0197458013003357?via%3Dihub. · DOI
  36. Huynh K, Lim WLF, Giles C, Jayawardana KS, Salim A, Mellett NA, et al. Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease. Nat Commun. 2020;11:5698. · DOI · Paper page
  37. Liu Q, Zhang J. Lipid metabolism in Alzheimer’s disease. Neurosci Bull [Internet]. 2014;30:331–45. Available from: http://link.springer.com/https://doi.org/10.1007/s12264-013-1410-3. · DOI · Paper page
  38. Tan ST, Ramesh T, Toh XR, Nguyen LN. Emerging roles of lysophospholipids in health and disease. Prog Lipid Res. 2020;80:101068. · DOI
  39. Sagy-Bross C, Hadad N, Levy R. Cytosolic phospholipase A2α upregulation mediates apoptotic neuronal death induced by aggregated amyloid-β peptide 1–42. Neurochem Int. 2013;63:541–50. · DOI
  40. Sabogal-Guáqueta AM, Villamil-Ortiz JG, Arias-Londoño JD, Cardona-Gómez GP. Inverse Phosphatidylcholine/Phosphatidylinositol Levels as Peripheral Biomarkers and Phosphatidylcholine/Lysophosphatidylethanolamine-Phosphatidylserine as hippocampal Indicator of Postischemic Cognitive impairment in rats. Front Neurosci. 2018;12. · DOI
  41. Tzekov R, Dawson C, Orlando M, Mouzon B, Reed J, Evans J et al. Sub-Chronic Neuropathological and Biochemical Changes in Mouse Visual System after Repetitive Mild Traumatic Brain Injury. Chidlow G, editor. PLoS One. 2016;11:e0153608. · DOI
  42. Palavicini JP, Wang C, Chen L, Hosang K, Wang J, Tomiyama T, et al. Oligomeric amyloid-beta induces MAPK-mediated activation of brain cytosolic and calcium-independent phospholipase A2 in a spatial-specific manner. Acta Neuropathol Commun. 2017;5:56. · DOI
  43. Sheikh AM, Nagai A. Lysophosphatidylcholine modulates fibril formation of amyloid beta peptide. FEBS J. 2011;278:634–42. · DOI
  44. Pedersen JN, Jiang Z, Christiansen G, Lee JC, Pedersen JS, Otzen DE. Lysophospholipids induce fibrillation of the repeat domain of Pmel17 through intermediate core-shell structures. Biochim et Biophys Acta (BBA) - Proteins Proteom. 2019;1867:519–28. · DOI
  45. Liu G-Y, Moon SH, Jenkins CM, Sims HF, Guan S, Gross RW. A functional role for eicosanoid-lysophospholipids in activating monocyte signaling. J Biol Chem. 2020;295:12167–80. · DOI
  46. Xu J, Wang T, Wu Y, Jin W, Wen Z. Microglia colonization of developing zebrafish midbrain is promoted by Apoptotic Neuron and Lysophosphatidylcholine. Dev Cell. 2016;38:214–22. · DOI
  47. Greiner AJ, Richardson RJ, Worden RM, Ofoli RY. Influence of lysophospholipid hydrolysis by the catalytic domain of neuropathy target esterase on the fluidity of bilayer lipid membranes. Biochimica et Biophysica Acta (BBA) -. Biomembranes. 2010;1798:1533–9. · DOI
  48. Zilka N, Stozicka Z, Kovac A, Pilipcinec E, Bugos O, Novak M. Human misfolded truncated tau protein promotes activation of microglia and leukocyte infiltration in the transgenic rat model of tauopathy. J Neuroimmunol. 2009;209:16–25. · DOI
  49. Heneka MT, Carson MJ, Khoury J, El, Landreth GE, Brosseron F, Feinstein DL et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol [Internet]. 2015;14:388–405. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1474442215700165. · DOI · Paper page
  50. Olzmann JA, Carvalho P. Dynamics and functions of lipid droplets. Nat Rev Mol Cell Biol. 2019;20:137–55. · DOI · Paper page
  51. den Brok MH, Raaijmakers TK, Collado-Camps E, Adema GJ. Lipid Droplets as Immune Modulators in Myeloid Cells. Trends Immunol [Internet]. 2018;39:380–92. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1471490618300231. · DOI · Paper page
  52. Nguyen TB, Louie SM, Daniele JR, Tran Q, Dillin A, Zoncu R et al. DGAT1-Dependent Lipid Droplet Biogenesis Protects Mitochondrial Function during Starvation-Induced Autophagy. Dev Cell [Internet]. 2017;42:9–21.e5. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1534580717304598. · DOI · Paper page
  53. Asai H, Ikezu S, Woodbury ME, Yonemoto GMS, Cui L, Ikezu T. Accelerated neurodegeneration and Neuroinflammation in transgenic mice expressing P301L tau mutant and Tau-Tubulin Kinase 1. Am J Pathol. 2014;184:808–18. · DOI
  54. Tu R, Yang W, Hu Z. Inhibition of sphingomyelin synthase 1 affects ceramide accumulation and hydrogen peroxide-induced apoptosis in Neuro-2a cells. NeuroReport. 2016;27:967–73. · DOI
  55. Malaplate-Armand C, Florent-Béchard S, Youssef I, Koziel V, Sponne I, Kriem B, et al. Soluble oligomers of amyloid-β peptide induce neuronal apoptosis by activating a cPLA2-dependent sphingomyelinase-ceramide pathway. Neurobiol Dis. 2006;23:178–89. · DOI
  56. Mielke MMMM, Haughey NJNJ, Bandaru VVR, Zetterberg H, Blennow K, Andreasson U, et al. Cerebrospinal fluid sphingolipids, β-amyloid, and tau in adults at risk for Alzheimer’s disease. Neurobiol Aging. 2014;35:2486–94. · DOI
  57. Murray NR, Fields AP. Phosphatidylglycerol is a physiologic activator of nuclear protein kinase C. J Biol Chem. 1998;273:11514–20. · DOI
  58. Muraleedharan A, Rotem-Dai N, Strominger I, Anto NP, Isakov N, Monsonego A, et al. Protein kinase C eta is activated in reactive astrocytes of an Alzheimer’s disease mouse model: evidence for its immunoregulatory function in primary astrocytes. Glia. 2021;69:697–714. · DOI
  59. Kim H-Y, Huang BX, Spector AA. Phosphatidylserine in the brain: metabolism and function. Prog Lipid Res. 2014;56:1–18. · DOI · Paper page
  60. Correas I, Díaz-Nido J, Avila J. Microtubule-associated protein tau is phosphorylated by protein kinase C on its tubulin binding domain. J Biol Chem. 1992;267:15721–8. · DOI
  61. Zhang X, Liu W, Cao Y, Tan W. Hippocampus Proteomics and Brain Lipidomics Reveal Network Dysfunction and Lipid Molecular Abnormalities in APP/PS1 mouse model of Alzheimer’s Disease. J Proteome Res. 2020;19:3427–37. · DOI
  62. Nitsch RM, Blusztajn JK, Pittas AG, Slack BE, Growdon JH, Wurtman RJ. Evidence for a membrane defect in Alzheimer disease brain. Proc Natl Acad Sci U S A. 1992;89:1671–5. · DOI
  63. Kopeikina KJ, Carlson GA, Pitstick R, Ludvigson AE, Peters A, Luebke JI, et al. Tau Accumulation causes mitochondrial distribution deficits in neurons in a mouse model of Tauopathy and in human Alzheimer’s Disease Brain. Am J Pathol. 2011;179:2071–82. · DOI
  64. Melov S, Adlard PA, Morten K, Johnson F, Golden TR, Hinerfeld D, et al. Mitochondrial oxidative stress causes hyperphosphorylation of tau. Khoury J El Editor PLoS One. 2007;2:e536. · DOI · Paper page
  65. Ramírez Ríos S, Lamarche F, Cottet-Rousselle C, Klaus A, Tuerk R, Thali R et al. Regulation of brain-type creatine kinase by AMP-activated protein kinase: Interaction, phosphorylation and ER localization. Biochimica et Biophysica Acta (BBA) - Bioenergetics [Internet]. 2014;1837:1271–83. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0005272814001091. · DOI
  66. Fecher C, Trovò L, Müller SA, Snaidero N, Wettmarshausen J, Heink S, et al. Cell-type-specific profiling of brain mitochondria reveals functional and molecular diversity. Nat Neurosci. 2019;22:1731–42. · DOI
  67. Eraso-Pichot A, Brasó-Vives M, Golbano A, Menacho C, Claro E, Galea E, et al. GSEA of mouse and human mitochondriomes reveals fatty acid oxidation in astrocytes. Glia. 2018;66:1724–35. · DOI
  68. Schönfeld P, Reiser G. Brain energy metabolism spurns fatty acids as fuel due to their inherent mitotoxicity and potential capacity to unleash neurodegeneration. Neurochem Int [Internet]. 2017;109:68–77. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0197018617301092. · DOI · Paper page
  69. Pan X, Nasaruddin M, Bin, Elliott CT, McGuinness B, Passmore AP, Kehoe PG, et al. Alzheimer’s disease–like pathology has transient effects on the brain and blood metabolome. Neurobiol Aging. 2016;38:151–63. · DOI
  70. Longo N, Frigeni M, Pasquali M. Carnitine transport and fatty acid oxidation. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research [Internet]. 2016;1863:2422–35. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0167488916300131. · DOI
  71. Abdul HM, Calabrese V, Calvani M, Butterfield DA. Acetyl-L-carnitine-induced up-regulation of heat shock proteins protects cortical neurons against amyloid-beta peptide 1–42-mediated oxidative stress and neurotoxicity: Implications for Alzheimer’s disease. J Neurosci Res [Internet]. 2006;84:398–408. Available from: https://onlinelibrary.wiley.com/doi/https://doi.org/10.1002/jnr.20877. · DOI
  72. Manzo E, O’Conner AG, Barrows JM, Shreiner DD, Birchak GJ, Zarnescu DC. Medium-chain fatty acids, Beta-hydroxybutyric acid and genetic modulation of the Carnitine Shuttle are Protective in a Drosophila model of ALS based on TDP-43. Front Mol Neurosci. 2018;11. · DOI

Cited by

Sorted by citations

Metadata

Authors
Olešová, D., Dobešová, D., Majerová, P., Brumarová, R., Kvasnička, A., Kouřil, Š., Stevens, E., Hanes, J., Fialová, Ľ., Michalicová, A., Piešťanský, J., Šinský, J., Kaňovský, P., Friedecký, D., & Kováč, A.
Venue
Journal of Neuroinflammation
Publisher
Springer Science and Business Media LLC
Published
2024-03-27
Volume
21
Issue
1
ISSN
1742-2094
DOI
10.1186/s12974-024-03060-4
PMC
PMC10976809
Cited by
33
References
7
Language
en
Licence
Funders
  • Agentúra na Podporu Výskumu a Vývoja (22-0313, 21-0321)
  • Agentúra Ministerstva Školstva, Vedy, Výskumu a Športu SR (2/0129/21)
  • University Hospital Olomouc (MHCZ-DRO FNOL 00098892)
  • University Palacky Olomouc (DSGC-2021-0098)

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