CoChat
Sign Up
Cited by 83Gut microbiota and healthAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

Transmission of Alzheimer’s disease-associated microbiota dysbiosis and its impact on cognitive function: evidence from mice and patients

Open access
Zhang, Yiying, Shen, Yuan, Liufu, Ning, Liu, Ling, Li, Wei, Shi, Zhongyong, Zheng, Hailin, Mei, Xinchun +11 more·2023·Molecular Psychiatry
DOI 10.1038/s41380-023-02216-7PMC PMC11733706

Published version of a preprint

Open this paper in CoChat — free accountOpen PDF

Abstract

Spouses of Alzheimer's disease (AD) patients are at a higher risk of developing incidental dementia. However, the causes and underlying mechanism of this clinical observation remain largely unknown. One possible explanation is linked to microbiota dysbiosis, a condition that has been associated with AD. However, it remains unclear whether gut microbiota dysbiosis can be transmitted from AD individuals to non-AD individuals and contribute to the development of AD pathogenesis and cognitive impairment. We, therefore, set out to perform both animal studies and clinical investigation by co-housing wild-type mice and AD transgenic mice, analyzing microbiota via 16S rRNA gene sequencing, measuring short-chain fatty acid amounts, and employing behavioral test, mass spectrometry, site-mutations and other methods. The present study revealed that co-housing between wild-type mice and AD transgenic mice or administrating feces of AD transgenic mice to wild-type mice resulted in AD-associated gut microbiota dysbiosis, Tau phosphorylation, and cognitive impairment in the wild-type mice. Gavage with Lactobacillus and Bifidobacterium restored these changes in the wild-type mice. The oral and gut microbiota of AD patient partners resembled that of AD patients but differed from healthy controls, indicating the transmission of microbiota. The underlying mechanism of these findings includes that the butyric acid-mediated acetylation of GSK3β at lysine 15 regulated its phosphorylation at serine 9, consequently impacting Tau phosphorylation. Pending confirmative studies, these results provide insight into a potential link between the transmission of AD-associated microbiota dysbiosis and development of cognitive impairment, which underscore the need for further research in this area.

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 · 10.1038/s41380-023-02216-7

Cites

20 of 20 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?

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: 78

  1. [2]Selkoe DJ. Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev. 2001; 81: 741– 66. 11274343
  2. [3]Grundke-Iqbal I, Iqbal K, Quinlan M, Tung YC, Zaidi MS, Wisniewski HM. Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J Biol Chem. 1986; 261: 6084– 9. 3084478
  3. [4]Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA. 1986; 83: 4913– 7. 3088567 PMC323854
  4. [5]Trojanowski JQ, Lee VM. Paired helical filament tau in Alzheimer’s disease. The kinase connection. Am J Pathol. 1994; 144: 449– 53. 8129030 PMC1887092
  5. [6]Buee L, Bussiere T, Buee-Scherrer V, Delacourte A, Hof PR. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev. 2000; 33: 95– 130. 10967355
  6. [7]Holtzman DM, Carrillo MC, Hendrix JA, Bain LJ, Catafau AM, Gault LM, Tau from research to clinical development. Alzheimers Dement. 2016; 12: 1033– 9. 27154059
  7. [8]Wang Y, Mandelkow E. Tau in physiology and pathology. Nat Rev Neurosci. 2016; 17: 5– 21. 26631930
  8. [10]Calsolaro V, Edison P. Neuroinflammation in Alzheimer’s disease: current evidence and future directions. Alzheimers Dement. 2016; 12: 719– 32. 27179961
  9. [12]Long-Smith C, O’Riordan KJ, Clarke G, Stanton C, Dinan TG, Cryan JF. Microbiota-gut-brain axis: new therapeutic opportunities. Annu Rev Pharm Toxicol. 2020; 60: 477– 502. 31506009
  10. [14]Liu L, Huh JR, Shah K. Microbiota and the gut-brain-axis: Implications for new therapeutic design in the CNS. EBioMedicine. 2022; 77:103908. PMC8897630 35255456
  11. [17]Zhuang ZQ, Shen LL, Li WW, Fu X, Zeng F, Gui L, Gut microbiota is altered in patients with Alzheimer’s disease. J Alzheimers Dis. 2018; 63: 1337– 46. 29758946
  12. [18]Zhu X, Li B, Lou P, Dai T, Chen Y, Zhuge A, The relationship between the gut microbiome and neurodegenerative diseases. Neurosci Bull. 2021; 37: 1510– 22. 34216356 PMC8490573
  13. [19]Cattaneo A, Cattane N, Galluzzi S, Provasi S, Lopizzo N, Festari C, Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol Aging. 2017; 49: 60– 68. 27776263
  14. [20]Vogt NM, Kerby RL, Dill-McFarland KA, Harding SJ, Merluzzi AP, Johnson SC, Gut microbiome alterations in Alzheimer’s disease. Sci Rep. 2017; 7: 13537. 29051531 PMC5648830
  15. [21]Liu P, Wu L, Peng G, Han Y, Tang R, Ge J, Altered microbiomes distinguish Alzheimer’s disease from amnestic mild cognitive impairment and health in a Chinese cohort. Brain Behav Immun. 2019; 80: 633– 43. 31063846
  16. [22]Shen L, Liu L, Ji HF. Alzheimer’s disease histological and behavioral manifestations in transgenic mice correlate with specific gut microbiome state. J Alzheimers Dis. 2017; 56: 385– 90. 27911317
  17. [23]Chen Y, Fang L, Chen S, Zhou H, Fan Y, Lin L, Gut microbiome alterations precede cerebral amyloidosis and microglial pathology in a mouse model of Alzheimer’s disease. Biomed Res Int. 2020; 2020:8456596. PMC7273394 32596386
  18. [25]Cuervo-Zanatta D, Garcia-Mena J, Perez-Cruz C. Gut microbiota alterations and cognitive impairment are sexually dissociated in a transgenic mice model of Alzheimer’s disease. J Alzheimers Dis. 2021; 82: S195– S214. 33492296
  19. [26]Harach T, Marungruang N, Duthilleul N, Cheatham V, Mc Coy KD, Frisoni G, Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota. Sci Rep. 2017; 7: 41802. 28176819 PMC5297247
  20. [27]Brandscheid C, Schuck F, Reinhardt S, Schafer KH, Pietrzik CU, Grimm M, Altered gut microbiome composition and tryptic activity of the 5xFAD Alzheimer’s mouse model. J Alzheimers Dis. 2017; 56: 775– 88. 28035935
  21. [28]Marriage Williams C. and mental health: when a spouse has Alzheimer’s disease. Arch Psychiatr Nurs. 2011; 25: 220– 2 21621735
  22. [29]Lee S, Kawachi I, Grodstein F. Does caregiving stress affect cognitive function in older women? J Nerv Ment Dis. 2004; 192: 51– 7. 14718776
  23. [30]Vitaliano PP, Echeverria D, Yi J, Phillips PE, Young H, Siegler IC. Psychophysiological mediators of caregiver stress and differential cognitive decline. Psychol Aging. 2005; 20: 402– 11. 16248700
  24. [31]de Vugt ME, Jolles J, van Osch L, Stevens F, Aalten P, Lousberg R, Cognitive functioning in spousal caregivers of dementia patients: findings from the prospective MAASBED study. Age Ageing. 2006; 35: 160– 6. 16495293
  25. [32]Mackenzie CS, Smith MC, Hasher L, Leach L, Behl P. Cognitive functioning under stress: evidence from informal caregivers of palliative patients. J Palliat Med. 2007; 10: 749– 58. 17592987 PMC1905830
  26. [33]Norton MC, Smith KR, Ostbye T, Tschanz JT, Corcoran C, Schwartz S, Greater risk of dementia when spouse has dementia? The Cache County study. J Am Geriatr Soc. 2010; 58: 895– 900. 20722820 PMC2945313
  27. [34]Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012; 13: 701– 12. 22968153
  28. [35]Ma Y, Ajnakina O, Steptoe A, Cadar D. Higher risk of dementia in English older individuals who are overweight or obese. Int J Epidemiol. 2020; 49: 1353– 65. 32575116 PMC7660153
  29. [37]Grant WB. Using multicountry ecological and observational studies to determine dietary risk factors for Alzheimer’s disease. J Am Coll Nutr. 2016; 35: 476– 89. 27454859
  30. [38]Yusufov M, Weyandt LL, Piryatinsky I. Alzheimer’s disease and diet: a systematic review. Int J Neurosci. 2017; 127: 161– 75. 26887612
  31. [39]Musiek ES, Holtzman DM. Three dimensions of the amyloid hypothesis: time, space and ‘wingmen’. Nat Neurosci. 2015; 18: 800– 6. 26007213 PMC4445458
  32. [40]Hatfield CF, Herbert J, van Someren EJ, Hodges JR, Hastings MH. Disrupted daily activity/rest cycles in relation to daily cortisol rhythms of home-dwelling patients with early Alzheimer’s dementia. Brain. 2004; 127: 1061– 74. 14998915
  33. [41]Kumar D, Koyanagi I, Carrier-Ruiz A, Vergara P, Srinivasan S, Sugaya Y, Sparse activity of hippocampal adult-born neurons during REM sleep is necessary for memory consolidation. Neuron. 2020; 107: 552– 65.e510 32502462
  34. [42]Meng Q, Lin MS, Tzeng IS. Relationship between exercise and alzheimer’s disease: a narrative literature review. Front Neurosci. 2020; 14: 131. 32273835 PMC7113559
  35. [43]Maass A, Duzel S, Goerke M, Becke A, Sobieray U, Neumann K, Vascular hippocampal plasticity after aerobic exercise in older adults. Mol Psychiatry. 2015; 20: 585– 93. 25311366
  36. [44]Chandra S, Sisodia SS, Vassar RJ. The gut microbiome in Alzheimer’s disease: what we know and what remains to be explored. Mol Neurodegener. 2023; 18: 9. 36721148 PMC9889249
  37. [47]Dodiya HB, Lutz HL, Weigle IQ, Patel P, Michalkiewicz J, Roman-Santiago CJ, Gut microbiota-driven brain Abeta amyloidosis in mice requires microglia. J Exp Med. 2022; 219:e20200895. PMC8647415 34854884
  38. [50]Dodiya HB, Frith M, Sidebottom A, Cao Y, Koval J, Chang E, Synergistic depletion of gut microbial consortia, but not individual antibiotics, reduces amyloidosis in APPPS1–21 Alzheimer’s transgenic mice. Sci Rep. 2020; 10: 8183. 32424118 PMC7235236
  39. [51]Amaral AC, Perez-Nievas BG, Siao Tick Chong M, Gonzalez-Martinez A, Argente-Escrig H, Rubio-Guerra S, Isoform-selective decrease of glycogen synthase kinase-3-beta (GSK-3beta) reduces synaptic tau phosphorylation, transcellular spreading, and aggregation. iScience. 2021; 24:102058. PMC7848608 33554064
  40. [52]Sarikhani M, Mishra S, Maity S, Kotyada C, Wolfgeher D, Gupta MP, SIRT2 deacetylase regulates the activity of GSK3 isoforms independent of inhibitory phosphorylation. Elife. 2018; 7:e32952. PMC5860870 29504933
  41. [54]Westfall S, Caracci F, Estill M, Frolinger T, Shen L, Pasinetti GM. Chronic stress-induced depression and anxiety priming modulated by gut-brain-axis immunity. Front Immunol. 2021; 12:670500. PMC8264434 34248950
  42. [55]Gungor B, Adiguzel E, Gursel I, Yilmaz B, Gursel M. Intestinal microbiota in patients with spinal cord injury. PLoS ONE. 2016; 11:e0145878. PMC4709077 26752409
  43. [56]Qu D, Sun F, Feng S, Yu L, Tian F, Zhang H, Protective effects of Bacteroides fragilis against lipopolysaccharide-induced systemic inflammation and their potential functional genes. Food Funct. 2022; 13: 1015– 25. 35015021
  44. [57]D’Amato A, Di Cesare Mannelli L, Lucarini E, Man AL, Le Gall G, Branca JJV, Faecal microbiota transplant from aged donor mice affects spatial learning and memory via modulating hippocampal synaptic plasticity- and neurotransmission-related proteins in young recipients. Microbiome. 2020; 8: 140. 33004079 PMC7532115
  45. [58]Xu SS, Wang N, Huang L, Zhang XL, Feng ST, Liu SS, Changes in the mucosa-associated microbiome and transcriptome across gut segments are associated with obesity in a metabolic syndrome porcine model. Microbiol Spectr. 2022; 10:e0071722. PMC9430857 35862956
  46. [59]Liang JQ, Li T, Nakatsu G, Chen YX, Yau TO, Chu E, A novel faecal Lachnoclostridium marker for the non-invasive diagnosis of colorectal adenoma and cancer. Gut. 2020; 69: 1248– 57. 31776231 PMC7306980
  47. [60]Chen X, Levy JM, Hou A, Winters C, Azzam R, Sousa AA, PSD-95 family MAGUKs are essential for anchoring AMPA and NMDA receptor complexes at the postsynaptic density. Proc Natl Acad Sci USA. 2015; 112: E6983– 6992. 26604311 PMC4687590
  48. [62]Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chetelat G, Teunissen CE, Alzheimer’s disease. Lancet. 2021; 397: 1577– 90. 33667416 PMC8354300
  49. [63]Lopez-Almela I, Romani-Perez M, Bullich-Vilarrubias C, Benitez-Paez A, Gomez Del EM, Frances R, Bacteroides uniformis combined with fiber amplifies metabolic and immune benefits in obese mice. Gut Microbes. 2021; 13: 1– 20. PMC8018257 33499721
  50. [64]Lee HB, Do MH, Jhun H, Ha SK, Song HS, Roh SW, Amelioration of hepatic steatosis in mice through Bacteroides uniformis CBA7346-mediated regulation of high-fat diet-induced insulin resistance and lipogenesis. Nutrients. 2021; 13: 2989. 34578867 PMC8471872
  51. [65]Burrichter AG, Dorr S, Bergmann P, Haiss S, Keller A, Fournier C, Bacterial microcompartments for isethionate desulfonation in the taurine-degrading human-gut bacterium Bilophila wadsworthia. BMC Microbiol. 2021; 21: 340. 34903181 PMC8667426
  52. [66]Gunalan A, Biswas R, Sridharan B, Elamurugan TP. Pathogenic potential of Parabacteroides distasonis revealed in a splenic abscess case: a truth unfolded. BMJ Case Rep. 2020; 13:e236701. PMC7737074 33318274
  53. [67]De Vadder F, Kovatcheva-Datchary P, Goncalves D, Vinera J, Zitoun C, Duchampt A, Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell. 2014; 156: 84– 96. 24412651
  54. [69]Braniste V, Al-Asmakh M, Kowal C, Anuar F, Abbaspour A, Toth M, The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med. 2014; 6:263ra158. PMC4396848 25411471
  55. [70]Wachsmuth HR, Weninger SN, Duca FA. Role of the gut-brain axis in energy and glucose metabolism. Exp Mol Med. 2022; 54: 377– 92. 35474341 PMC9076644
  56. [72]Segain JP, Raingeard de la Bletiere D, Bourreille A, Leray V, Gervois N, Rosales C, Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn’s disease. Gut. 2000; 47: 397– 403. 10940278 PMC1728045
  57. [73]Sun J, Wang F, Li H, Zhang H, Jin J, Chen W, Neuroprotective effect of sodium butyrate against cerebral ischemia/reperfusion injury in mice. Biomed Res Int. 2015; 2015:395895. PMC4439479 26064905
  58. [75]Sarubbo F, Cavallucci V, Pani G. The Influence of Gut Microbiota on Neurogenesis: evidence and Hopes. Cells. 2022; 11: 382. 35159192 PMC8834402
  59. [76]Miko E, Csaszar A, Bodis J, Kovacs K. The maternal-fetal gut microbiota axis: physiological changes, dietary influence, and modulation possibilities. Life. 2022; 12: 424. 35330175 PMC8955030
  60. [78]Maqsood R, Rodgers R, Rodriguez C, Handley SA, Ndao IM, Tarr PI, Discordant transmission of bacteria and viruses from mothers to babies at birth. Microbiome. 2019; 7: 156. 31823811 PMC6902606
  61. [79]Ferretti P, Pasolli E, Tett A, Asnicar F, Gorfer V, Fedi S, Mother-to-infant microbial transmission from different body sites shapes the developing infant gut microbiome. Cell Host Microbe. 2018; 24: 133– 45.e135 30001516 PMC6716579
  62. [80]Inczefi O, Bacquie V, Olier-Pierre M, Rincel M, Ringot-Destrez B, Ellero-Simatos S, Targeted intestinal tight junction hyperpermeability alters the microbiome, behavior, and visceromotor responses. Cell Mol Gastroenterol Hepatol. 2020; 10: 206– 8.e203 32147490 PMC7296230
  63. [81]Abraham C, Abreu MT, Turner JR. Pattern recognition receptor signaling and cytokine networks in microbial defenses and regulation of intestinal barriers: implications for inflammatory bowel disease. Gastroenterology. 2022; 162: 1602– 16.e1606 35149024 PMC9112237
  64. [82]Browne HP, Neville BA, Forster SC, Lawley TD. Transmission of the gut microbiota: spreading of health. Nat Rev Microbiol. 2017; 15: 531– 43. 28603278 PMC5837012
  65. [83]Brito IL, Gurry T, Zhao S, Huang K, Young SK, Shea TP, Transmission of human-associated microbiota along family and social networks. Nat Microbiol. 2019; 4: 964– 71. 30911128 PMC7450247
  66. [85]Valles-Colomer M, Blanco-Miguez A, Manghi P, Asnicar F, Dubois L, Golzato D, The person-to-person transmission landscape of the gut and oral microbiomes. Nature. 2023; 614: 125– 35. 36653448 PMC9892008
  67. [86]Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J. 2017; 474: 1823– 36. 28512250 PMC5433529
  68. [88]Dawson HN, Cantillana V, Jansen M, Wang H, Vitek MP, Wilcock DM, Loss of tau elicits axonal degeneration in a mouse model of Alzheimer’s disease. Neuroscience. 2010; 169: 516– 31. 20434528 PMC2900546
  69. [89]Shen S, Lim G, You Z, Ding W, Huang P, Ran C, Gut microbiota is critical for the induction of chemotherapy-induced pain. Nat Neurosci. 2017; 20: 1213– 6. 28714953 PMC5575957
  70. [90]Kaliannan K, Wang B, Li XY, Kim KJ, Kang JX. A host-microbiome interaction mediates the opposing effects of omega-6 and omega-3 fatty acids on metabolic endotoxemia. Sci Rep. 2015; 5: 11276. 26062993 PMC4650612
  71. [91]Prizont R, Konigsberg N. Identification of bacterial glycosidases in rat cecal contents. Dig Dis Sci. 1981; 26: 773– 7. 6793336
  72. [92]Yang S, Gu C, Mandeville, Dong Y, Esposito E, Zhang Y, Aneshethesia and surgery impair blood-brain barrier and cogntive function in mice. Front Immunol. 2017; 8: 902. 28848542 PMC5552714
  73. [93]Liufu N, Liu L, Shen S, Jiang Z, Dong Y, Wang Y, Anesthesia and surgery induce age-dependent changes in behaviors and microbiota. Aging. 2020; 12: 1965– 86. 31974315 PMC7053599
  74. [94]Zhao G, Nyman M, Jonsson JA. Rapid determination of short-chain fatty acids in colonic contents and faeces of humans and rats by acidified water-extraction and direct-injection gas chromatography. Biomed Chromatogr. 2006; 20: 674– 82. 16206138
  75. [95]Lai Z, Shan W, Li J, Min J, Zeng X, Zuo Z. Appropriate exercise level attenuates gut dysbiosis and valeric acid increase to improve neuroplasticity and cognitive function after surgery in mice. Mol Psychiatry. 2021; 26: 7167– 87. 34663905 PMC8873004
  76. [96]Zhang Y, Xu Z, Wang H, Dong Y, Shi HN, Culley DJ, Anesthetics isoflurane and desflurane differently affect mitochondrial function, learning, and memory. Ann Neurol. 2012; 71: 687– 98. 22368036 PMC3942786
  77. [97]Aebersold R, Goodlett DR. Mass spectrometry in proteomics. Chem Rev. 2001; 101: 269– 95. 11712248
  78. [98]Li H, Jia J, Yang Z. Mini-Mental state examination in elderly chinese: a population-based normative study. J Alzheimers Dis. 2016; 53: 487– 96. 27163822

Cited by

Sorted by citations

Authors
Zhang, Y., Shen, Y., Liufu, N., Liu, L., Li, W., Shi, Z., Zheng, H., Mei, X., Chen, C.-Y., Jiang, Z., Abtahi, S., Dong, Y., Liang, F., Shi, Y., Cheng, L. L., Yang, G., Kang, J. X., Wilkinson, J. E., & Xie, Z.
Affiliations
  • Harvard University (US)
  • Tongji University (CN)
  • Shanghai Medical College of Fudan University (CN)
  • Columbia University Irving Medical Center (US)
Corresponding author
  • Zhang, Yiying
  • Xie, Zhongcong
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2023-08-21
Volume
28
Issue
10
Pages
4421-4437
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/s41380-023-02216-7
PMC
PMC11733706
OpenAlex
W4386028473
Cited by
83
References
20
Citations by year
2026: 24 · 2025: 28 · 2024: 23 · 2023: 8
FWCI
7.40
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Psychiatry (publishedVersion)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • PubMed Central (submittedVersion, cc-by)
Funders
Foundation for the National Institutes of Health (R21 AG065606, R01AG041274, R01AG062509, RF1070761)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, gut dysbiosis, cohousing, fecal microbiota transplantation, cognitive impairment, tau phosphorylation, butyrate, short-chain fatty acids, Lactobacillus, Bifidobacterium, transgenic mouse model

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