CoChat
Sign Up
Cited by 61Proteoglycans and glycosaminoglycans researchAlzheimer's disease research and treatmentsNeuroscience and Neuropharmacology Research

The “Loss” of Perineuronal Nets in Alzheimer's Disease: Missing or Hiding in Plain Sight?

Open access
Scarlett, Jarrad M., Hu, Shannon J., Alonge, Kimberly M.·2022·Frontiers in Integrative Neuroscience
DOI 10.3389/fnint.2022.896400PMC PMC9174696
Open this paper in CoChat — free accountOpen PDF

Abstract

Perineuronal nets (PNNs) are chondroitin-sulfate glycosaminoglycan (CS-GAG) containing extracellular matrix structures that assemble around neurons involved in learning, memory, and cognition. Owing to the unique patterning of negative charges stemming from sulfate modifications to the attached CS-GAGs, these matrices play key roles in mediating glycan-protein binding, signaling interactions, and charged ion buffering of the underlying circuitry. Histochemical loss of PNN matrices has been reported for a range of neurocognitive and neurodegenerative diseases, implying that PNNs might be a key player in the pathogenesis of neurological disorders. In this hypothesis and theory article, we begin by highlighting PNN changes observed in human postmortem brain tissue associated with Alzheimer's disease (AD) and corresponding changes reported in rodent models of AD neuropathology. We then discuss the technical limitations surrounding traditional methods for PNN analyses and propose alternative explanations to these historical findings. Lastly, we embark on a global re-evaluation of the interpretations for PNN changes across brain regions, across species, and in relation to other neurocognitive disorders.

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 · 10.3389/fnint.2022.896400

Cites

12 of 12 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?

  • AD-associated PNN loss is characterized by selective deglycosylation of PNN CSPGs instead of core protein degradation and total loss of PNN matrices.

    “These reports imply that AD-associated ‘PNN loss’ is characterized by selective deglycosylation of the PNN CSPGs instead of core protein degradation and total loss of the PNN matrices themselves (Scarlett et al. 2022).”

    From Perineuronal net deglycosylation associates with tauopathy‐induced gliosis and neurodegeneration (2024) · cites this paper as Scarlett et al. 2022

    The Figure 9 caption and Conclusions (page unavailable) propose that apparent PNN loss in AD may reflect remodeling rather than degradation of the entire matrix. They attribute reduced WFA labeling chiefly to altered CS-GAG sulfation and lectin recognition, not established selective deglycosylation. The claim therefore supports the matrix-remodeling distinction but overstates and misidentifies the proposed glycan mechanism. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • WFA binding affinity is highly influenced by the abundance of 0S-CS isomer units incorporated into the PNN CS-GAGs, and WFA should not be thought of as a universal, non-specific histological label for PNN CS-GAGs.

    “WFA binding affinity is highly influenced by the abundance of 0S-CS isomer units incorporated into the PNN CS-GAGs, and as such, should not be thought of as universal, non-specific histological label for PNN CS-GAGs (Scarlett et al. 2022; Härtig et al. 2022).”

    From Perineuronal net deglycosylation associates with tauopathy‐induced gliosis and neurodegeneration (2024) · cites this paper as Scarlett et al. 2022

  • The authors recently reported striking regional differences in brain CS-GAG composition throughout wt mouse brain tissue.

    “Indeed, we recently reported striking regional differences in brain CS-GAG composition throughout wt mouse brain tissue (Scarlett et al. 2022)”

    From Perineuronal net deglycosylation associates with tauopathy‐induced gliosis and neurodegeneration (2024) · cites this paper as Scarlett et al. 2022

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: 57

  1. Ajmo J. M. Bailey L. A. Howell M. D. Cortez L. K. Pennypacker K. R. Mehta H. N.. (2010). Abnormal post-translational and extracellular processing of brevican in plaque-bearing mice over-expressing APPsw. J. Neurochem. 113, 784– 795. 10.1111/j.1471-4159.2010.06647.x 20180882 PMC2855738 · DOI · Paper page
  2. Alcaide J. Guirado R. Crespo C. Blasco-Ibáñez J. M. Varea E. Sanjuan J.. (2019). Alterations of perineuronal nets in the dorsolateral prefrontal cortex of neuropsychiatric patients. Int. J. Bipolar Disord. 7, 24. 10.1186/s40345-019-0161-0 31728775 PMC6856240 · DOI · Paper page
  3. Alonge K. M. Herbert M. J. Yagi M. Cook D. G. Banks W. A. Logsdon A. F. (2021). Changes in brain matrix glycan sulfation associate with reactive gliosis and motor coordination in mice with head trauma. Front. Behav. Neurosci. 15, 745288. 10.3389/fnbeh.2021.745288 34776892 PMC8581466 · DOI · Paper page
  4. Alonge K. M. Logsdon A. F. Murphree T. A. Banks W. A. Keene C. D. Edgar J. S.. (2019). Quantitative analysis of chondroitin sulfate disaccharides from human and rodent fixed brain tissue by electrospray ionization-tandem mass spectrometry. Glycobiology 29, 847– 860. 10.1093/glycob/cwz060 31361007 PMC6861844 · DOI · Paper page
  5. Alonge K. M. Mirzadeh Z. Scarlett J. M. Logsdon A. F. Brown J. M. Cabrales E.. (2020). Hypothalamic perineuronal net assembly is required for sustained diabetes remission induced by fibroblast growth factor 1 in rats. Nat. Metab. 2, 1025– 1033. 10.1038/s42255-020-00275-6 32895577 PMC7572652 · DOI · Paper page
  6. Ariga T. Miyatake T. Yu R. K. (2010). Role of proteoglycans and glycosaminoglycans in the pathogenesis of Alzheimer's disease and related disorders: amyloidogenesis and therapeutic strategies–a review. J. Neurosci. Res. 88, 2303– 2315. 10.1002/jnr.22393 20623617 · DOI
  7. Baig S. Wilcock G. K. Love S. (2005). Loss of perineuronal net N-acetylgalactosamine in Alzheimer's disease. Acta Neuropathol. 110, 393– 401. 10.1007/s00401-005-1060-2 16133543 · DOI · Paper page
  8. Barahona R. A. Morabito S. Swarup V. Green K. N. (2022). Cortical diurnal rhythms remain intact with microglial depletion. Sci. Rep. 12, 114– 114. 10.1038/s41598-021-04079-w 34997092 PMC8742049 · DOI
  9. Bartolini B. Thelin M. A. Rauch U. Feinstein R. Oldberg A. Malmstrom A.. (2012). Mouse development is not obviously affected by the absence of dermatan sulfate epimerase 2 in spite of a modified brain dermatan sulfate composition. Glycobiology 22, 1007– 1016. 10.1093/glycob/cws065 22496542 · DOI
  10. Brückner G. Hausen D. Härtig W. Drlicek M. Arendt T. Brauer K. (1999). Cortical areas abundant in extracellular matrix chondroitin sulphate proteoglycans are less affected by cytoskeletal changes in Alzheimer's disease. Neuroscience 92, 791– 805. 10.1016/S0306-4522(99)00071-8 10426522 · DOI · Paper page
  11. Carulli D. Pizzorusso T. Kwok J. C. Putignano E. Poli A. Forostyak S.. (2010). Animals lacking link protein have attenuated perineuronal nets and persistent plasticity. Brain 133, 2331– 2347. 10.1093/brain/awq145 20566484 · DOI · Paper page
  12. Carulli D. Verhaagen J. (2021). An extracellular perspective on CNS maturation: perineuronal nets and the control of plasticity. Int. J. Mol. Sci. 22, 2434. 10.3390/ijms22052434 33670945 PMC7957817 · DOI
  13. Cattaud V. Bezzina C. Rey C. C. Lejards C. Dahan L. Verret L. (2018). Early disruption of parvalbumin expression and perineuronal nets in the hippocampus of the Tg2576 mouse model of Alzheimer's disease can be rescued by enriched environment. Neurobiol. Aging 72, 147– 158. 10.1016/j.neurobiolaging.2018.08.024 30273829 · DOI · Paper page
  14. Crapser J. D. Spangenberg E. E. Barahona R. A. Arreola M. A. Hohsfield L. A. Green K. N. (2020). Microglia facilitate loss of perineuronal nets in the Alzheimer's disease brain. eBioMedicine 58: 102919. 10.1016/j.ebiom.2020.102919 32745992 PMC7399129 · DOI · Paper page
  15. Dauth S. Grevesse T. Pantazopoulos H. Campbell P. H. Maoz B. M. Berretta S.. (2016). Extracellular matrix protein expression is brain region dependent. J. Comp. Neurol. 524, 1309– 1336. 10.1002/cne.23965 26780384 PMC7714387 · DOI
  16. Dewitt D. A. Silver J. Canning D. R. Perry G. (1993). Chondroitin sulfate proteoglycans are associated with the lesions of Alzheimer's disease. Exp. Neurol. 121, 149– 152. 10.1006/exnr.1993.1081 8339766 · DOI
  17. Djerbal L. Lortat-Jacob H. Kwok J. (2017). Chondroitin sulfates and their binding molecules in the central nervous system. Glycoconj. J. 34, 363– 376. 10.1007/s10719-017-9761-z 28101734 PMC5487772 · DOI · Paper page
  18. Gilbert R. J. Mckeon R. J. Darr A. Calabro A. Hascall V. C. Bellamkonda R. V. (2005). CS-4,6 is differentially upregulated in glial scar and is a potent inhibitor of neurite extension. Mol. Cell. Neurosci. 29, 545– 558. 10.1016/j.mcn.2005.04.006 15936953 · DOI
  19. Grothe M. J. Sepulcre J. Gonzalez-Escamilla G. Jelistratova I. Schöll M. Hansson O.. (2018). Molecular properties underlying regional vulnerability to Alzheimer's disease pathology. Brain 141, 2755– 2771. 10.1093/brain/awy189 30016411 PMC6113636 · DOI · Paper page
  20. Härtig W. Derouiche A. Welt K. Brauer K. Grosche J. Mäder M.. (1999). Cortical neurons immunoreactive for the potassium channel Kv3.1b subunit are predominantly surrounded by perineuronal nets presumed as a buffering system for cations. Brain Res. 842, 15– 29. 10.1016/S0006-8993(99)01784-9 10526091 · DOI · Paper page
  21. Hilbig H. Bidmon H. J. Blohm U. Zilles K. (2001). Wisteria floribunda agglutinin labeling patterns in the human cortex: a tool for revealing areal borders and subdivisions in parallel with immunocytochemistry. Anat. Embryol. 203, 45– 52. 10.1007/s004290000135 11195088 · DOI
  22. Howell M. D. Bailey L. A. Cozart M. A. Gannon B. M. Gottschall P. E. (2015). Hippocampal administration of chondroitinase ABC increases plaque-adjacent synaptic marker and diminishes amyloid burden in aged APPswe/PS1dE9 mice. Acta Neuropathol. Commun. 3, 54– 54. 10.1186/s40478-015-0233-z 26337292 PMC4559967 · DOI
  23. Hsiao K. Chapman P. Nilsen S. Eckman C. Harigaya Y. Younkin S.. (1996). Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 274, 99– 102. 10.1126/science.274.5284.99 8810256 · DOI · Paper page
  24. Huynh M. B. Ouidja M. O. Chantepie S. Carpentier G. Maïza A. Zhang G.. (2019). Glycosaminoglycans from Alzheimer's disease hippocampus have altered capacities to bind and regulate growth factors activities and to bind tau. PLoS ONE 14, e0209573. 10.1371/journal.pone.0209573 30608949 PMC6319808 · DOI · Paper page
  25. Javonillo D. I. Tran K. M. Phan J. Hingco E. Kramár E. A. Da Cunha C.. (2021). Systematic phenotyping and characterization of the 3xTg-AD mouse model of Alzheimer's disease. Front. Neurosci. 15, 785276. 10.1101/2021.10.01.462640 35140584 PMC8818877 · DOI
  26. Lendvai D. Morawski M. Négyessy L. Gáti G. Jäger C. Baksa G.. (2013). Neurochemical mapping of the human hippocampus reveals perisynaptic matrix around functional synapses in Alzheimer's disease. Acta Neuropathol. 125, 215– 229. 10.1007/s00401-012-1042-0 22961619 PMC6485544 · DOI · Paper page
  27. Lensjø K. K. Christensen A. C. Tennøe S. Fyhn M. Hafting T. (2017). Differential expression and cell-type specificity of perineuronal nets in hippocampus, medial entorhinal cortex, and visual cortex examined in the rat and mouse. eNeuro 4:ENEURO.0379-16. 10.1523/ENEURO.0379-16.2017 28593193 PMC5461557 · DOI · Paper page
  28. Liu Y.-J. Spangenberg E. E. Tang B. Holmes T. C. Green K. N. Xu X. (2021). Microglia elimination increases neural circuit connectivity and activity in adult mouse cortex. J. Neurosci. 41, 1274– 1287. 10.1523/JNEUROSCI.2140-20.2020 33380470 PMC7888230 · DOI
  29. Logsdon A. F. Francis K. L. Richardson N. E. Hu S. J. Faber C. L. Phan B. A.. (2021). Decoding perineuronal net glycan sulfation patterns in the Alzheimer's disease brain. Alzheimers Dement. 18, 942– 954. 10.1002/alz.12451 34482642 PMC8897514 · DOI
  30. Matthews R. T. Kelly G. M. Zerillo C. A. Gray G. Tiemeyer M. Hockfield S. (2002). Aggrecan glycoforms contribute to the molecular heterogeneity of perineuronal nets. J. Neurosci. 22, 7536– 7547. 10.1523/JNEUROSCI.22-17-07536.2002 12196577 PMC6757962 · DOI · Paper page
  31. Mauney S. A. Athanas K. M. Pantazopoulos H. Shaskan N. Passeri E. Berretta S.. (2013). Developmental pattern of perineuronal nets in the human prefrontal cortex and their deficit in schizophrenia. Biol. Psychiatry 74, 427– 435. 10.1016/j.biopsych.2013.05.007 23790226 PMC3752333 · DOI · Paper page
  32. Mckeon R. J. Jurynec M. J. Buck C. R. (1999). The chondroitin sulfate proteoglycans neurocan and phosphacan are expressed by reactive astrocytes in the chronic CNS glial scar. J. Neurosci. 19, 10778– 10788. 10.1523/JNEUROSCI.19-24-10778.1999 10594061 PMC6784959 · DOI · Paper page
  33. Mehta D. Jackson R. Paul G. Shi J. Sabbagh M. (2017). Why do trials for Alzheimer's disease drugs keep failing? A discontinued drug perspective for 2010-2015. Expert Opin. Investig. Drugs 26, 735– 739. 10.1080/13543784.2017.1323868 28460541 PMC5576861 · DOI
  34. Miyata S. Kitagawa H. (2016). Chondroitin 6-sulfation regulates perineuronal net formation by controlling the stability of aggrecan. Neural Plast. 2016, 1305801. 10.1155/2016/1305801 27057358 PMC4738747 · DOI · Paper page
  35. Miyata S. Nadanaka S. Igarashi M. Kitagawa H. (2018). Structural variation of chondroitin sulfate chains contributes to the molecular heterogeneity of perineuronal nets. Front. Integr. Neurosci. 12: 3. 10.3389/fnint.2018.00003 29456495 PMC5801575 · DOI
  36. Morawski M. Bruckner G. Jager C. Seeger G. Matthews R. T. Arendt T. (2012). Involvement of perineuronal and perisynaptic extracellular matrix in Alzheimer's disease neuropathology. Brain Pathol. 22, 547– 561. 10.1111/j.1750-3639.2011.00557.x 22126211 PMC3639011 · DOI · Paper page
  37. Morawski M. Pavlica S. Seeger G. Grosche J. Kouznetsova E. Schliebs R.. (2010b). Perineuronal nets are largely unaffected in Alzheimer model Tg2576 mice. Neurobiol. Aging 31, 1254– 1256. 10.1016/j.neurobiolaging.2008.07.023 18829133 · DOI
  38. Nadanaka S. Miyata S. Yaqiang B. Tamura J.-I. Habuchi O. Kitagawa H. (2020). Reconsideration of the semaphorin-3A binding motif found in chondroitin sulfate using galnac4s-6st-knockout mice. Biomolecules 10, 1499. 10.3390/biom10111499 33143303 PMC7694144 · DOI · Paper page
  39. Nicholson C. Syková E. (1998). Extracellular space structure revealed by diffusion analysis. Trends Neurosci. 21, 207– 215. 10.1016/S0166-2236(98)01261-2 9610885 · DOI · Paper page
  40. Pantazopoulos H. Gisabella B. Rexrode L. Benefield D. Yildiz E. Seltzer P.. (2020). Circadian rhythms of perineuronal net composition. eneuro 7, ENEURO.0034-0019.2020. 10.1523/ENEURO.0034-19.2020 32719104 PMC7405073 · DOI
  41. Pantazopoulos H. Katsel P. Haroutunian V. Chelini G. Klengel T. Berretta S. (2021). Molecular signature of extracellular matrix pathology in schizophrenia. Eur. J. Neurosci. 53, 3960– 3987. 10.1111/ejn.15009 33070392 PMC8359380 · DOI
  42. Pantazopoulos H. Markota M. Jaquet F. Ghosh D. Wallin A. Santos A.. (2015). Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala. Transl. Psychiatry 5,– e496. 10.1038/tp.2014.128 25603412 PMC4312825 · DOI · Paper page
  43. Pantazopoulos H. Woo T. U. Lim M. P. Lange N. Berretta S. (2010). Extracellular matrix-glial abnormalities in the amygdala and entorhinal cortex of subjects diagnosed with schizophrenia. Arch. Gen. Psychiatry 67, 155– 166. 10.1001/archgenpsychiatry.2009.196 20124115 PMC4208310 · DOI · Paper page
  44. Reichelt A. C. (2020). Is loss of perineuronal nets a critical pathological event in Alzheimer's disease? eBioMedicine 59: 102946. 10.1016/j.ebiom.2020.102946 32810826 PMC7452426 · DOI
  45. Rey C. C. Robert V. Bouisset G. Loisy M. Lopez S. Cattaud V.. (2022). Altered inhibitory function in hippocampal CA2 contributes in social memory deficits in Alzheimer's mouse model. iScience 25, 103895– 103895. 10.1016/j.isci.2022.103895 35243253 PMC8873612 · DOI
  46. Seeger G. Lüth H. J. Winkelmann E. Brauer K. (1996). Distribution patterns of Wisteria floribunda agglutinin binding sites and parvalbumin-immunoreactive neurons in the human visual cortex: a double-labelling study. J. Hirnforsch. 37, 351– 366. 8872558
  47. Shida M. Mikami T. Tamura J. I. Kitagawa H. (2019). Chondroitin sulfate-D promotes neurite outgrowth by acting as an extracellular ligand for neuronal integrin αVβ3. Biochim. Biophys. Acta Gen. Subj. 1863, 1319– 1331. 10.1016/j.bbagen.2019.06.004 31181256 · DOI · Paper page
  48. Shimizu H. Ghazizadeh M. Sato S. Oguro T. Kawanami O. (2009). Interaction between β-amyloid protein and heparan sulfate proteoglycans from the cerebral capillary basement membrane in Alzheimer's disease. J. Clin. Neurosci. 16, 277– 282. 10.1016/j.jocn.2008.04.009 19091577 · DOI
  49. Smith P. D. Coulson-Thomas V. J. Foscarin S. Kwok J. C. F. Fawcett J. W. (2015). “GAG-ing with the neuron”: the role of glycosaminoglycan patterning in the central nervous system. Exp. Neurol. 274, 100– 114. 10.1016/j.expneurol.2015.08.004 26277685 · DOI
  50. Syková E. Nicholson C. (2008). Diffusion in brain extracellular space. Physiol. Rev. 88, 1277– 1340. 10.1152/physrev.00027.2007 18923183 PMC2785730 · DOI · Paper page
  51. Testa D. Prochiantz A. Di Nardo A. A. (2019). Perineuronal nets in brain physiology and disease. Semin. Cell Dev. Biol. 89, 125– 135. 10.1016/j.semcdb.2018.09.011 30273653 · DOI
  52. Ueno H. Fujii K. Suemitsu S. Murakami S. Kitamura N. Wani K.. (2018). Expression of aggrecan components in perineuronal nets in the mouse cerebral cortex. IBRO Rep. 4, 22– 37. 10.1016/j.ibror.2018.01.002 30135949 PMC6084874 · DOI
  53. Vallet S. D. Clerc O. Ricard-Blum S. (2021). Glycosaminoglycan-protein interactions: the first draft of the glycosaminoglycan interactome. J. Histochem. Cytochem. 69, 93– 104. 10.1369/0022155420946403 32757871 PMC7841700 · DOI
  54. Végh M. J. Heldring C. M. Kamphuis W. Hijazi S. Timmerman A. J. Li K. W.. (2014). Reducing hippocampal extracellular matrix reverses early memory deficits in a mouse model of Alzheimer's disease. Acta Neuropathol. Commun. 2, 76. 10.1186/s40478-014-0076-z 24974208 PMC4149201 · DOI
  55. Virgintino D. Perissinotto D. Girolamo F. Mucignat M. T. Montanini L. Errede M.. (2009). Differential distribution of aggrecan isoforms in perineuronal nets of the human cerebral cortex. J. Cell. Mol. Med. 13, 3151– 3173. 10.1111/j.1582-4934.2009.00694.x 19220578 PMC4516474 · DOI
  56. Vitellaro-Zuccarello L. De Biasi S. Spreafico R. (1998). One hundred years of Golgi's “perineuronal net”: history of a denied structure. Ital. J. Neurol. Sci. 19, 249– 253. 10.1007/BF02427613 10933466 · DOI
  57. Yang S. Gigout S. Molinaro A. Naito-Matsui Y. Hilton S. Foscarin S.. (2021). Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing. Mol. Psychiatry 26, 5658– 5668. 10.1038/s41380-021-01208-9 34272488 PMC8758471 · DOI · Paper page

Cited by

Sorted by citations

Authors
Scarlett, J. M., Hu, S. J., & Alonge, K. M.
Affiliations
  • Seattle Children's Hospital (US)
  • University of Washington (US)
Corresponding author
Alonge, Kimberly M.
ORCID
Venue
Frontiers in Integrative Neuroscience
Publisher
Frontiers Media SA
Published
2022-05-25
Volume
16
Pages
896400-896400
ISSN
1662-5145 (ISSN-L)
DOI
10.3389/fnint.2022.896400
PMC
PMC9174696
OpenAlex
W4281482828
Cited by
61
References
12
Citations by year
2026: 14 · 2025: 20 · 2024: 15 · 2023: 9 · 2022: 3
FWCI
6.28
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Integrative Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK017047, DK114474, DK128383)
  • National Institute on Aging (AG066509, AG074152)
  • U.S. Department of Defense (W81XWH2110635)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
perineuronal nets, Alzheimer's disease, extracellular matrix, postmortem brain, neurodegeneration, neurocognitive disorders, regional brain differences, species differences

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