The DOI matches its Crossref record; 63 of the 64 references it cites were found in a registry or an index.
Widespread cell stress and mitochondrial dysfunction occur in patients with early Alzheimer’s disease
Open accessPublished version of a preprint
Abstract
Abstract Cell stress and impaired oxidative phosphorylation are central to mechanisms of synaptic loss and neurodegeneration in the cellular pathology of Alzheimer’s disease (AD). We quantified the in vivo density of the endoplasmic reticulum stress marker, the sigma 1 receptor (S1R) using [ 11 C]SA4503 PET, as well as that of mitochondrial complex I (MC1) with [ 18 F]BCPP-EF and the pre-synaptic vesicular protein SV2A with [ 11 C]UCB-J in 12 patients with early AD and in 16 cognitively normal controls. We integrated these molecular measures with assessments of regional brain volumes and brain perfusion (CBF) measured with MRI arterial spin labelling. 8 AD patients were followed longitudinally to estimate rates of change with disease progression over 12-18 months. The AD patients showed widespread increases in S1R (≤ 27%) and regional decreases in MC1 (≥ -28%), SV2A (≥ -25%), brain volume (≥ -23%), and CBF (≥ -26%). [ 18 F]BCPP-EF PET MC1 density (≥ -12%) and brain volumes (≥ -5%) were further reduced at follow up in brain regions consistent with the differences between AD patients and controls at baseline. Exploratory analyses showing associations of MC1, SV2A and S1R density with cognitive changes at baseline and longitudinally with AD, but not in controls, suggested a loss of metabolic functional reserve with disease. Our study thus provides novel in vivo evidence for widespread cellular stress and bioenergetic abnormalities in early AD and that they may be clinically meaningful.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“Human in vivo studies with synaptic vesicle glycoprotein 2a–binding PET ligands confirm this loss of synaptic density. 54”
From Alzheimer's disease and its progression reduce pyramidal cell gain and connectivity (2025) · cites this paper as [54]
Citations
Cites
Advances in functional and structural MR image analysis and implementation as FSL
Smith, S. M., Jenkinson, M., Woolrich, M. W., Beckmann, C. F., Behrens, T. E. J., Johansen-Berg, H., Bannister, P. R., De Luca, M., Drobnjak, I., Flitney, D. E., et al. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2004.07.051 · Cited by 13,630
Self-citationJenkinson, M., Bannister, P., Brady, M., & Smith, S. (2002) · NeuroImage · doi:10.1006/nimg.2002.1132 · Cited by 11,888
Alzheimer's disease: the amyloid cascade hypothesis
Hardy, J. A., & Higgins, G. A. (1992) · Science · doi:10.1126/science.1566067 · Cited by 7,484
Cognitive reserve in ageing and Alzheimer's disease
Stern, Y. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70191-6 · Cited by 3,557 · cited 1×
“The healthy brain thus has considerable functional reserve arising from a redundancy or plasticity that allows normal cognition to be maintained despite some impairments of functions (those affecting metabolism and synaptic and neuronal circuit activity) (20).”
BackgroundPhases of Aβ-deposition in the human brain and its relevance for the development of AD
Thal, D. R., Rüb, U., Orantes, M., & Braak, H. (2002) · Neurology · doi:10.1212/wnl.58.12.1791 · Cited by 3,490
The molecular pathology of Alzheimer's disease
Selkoe, D. J. (1991) · Neuron · doi:10.1016/0896-6273(91)90052-2 · Cited by 2,708
Single-cell transcriptomic analysis of Alzheimer’s disease
Mathys, H., Davila-Velderrain, J., Peng, Z., Gao, F., Mohammadi, S., Young, J. Z., Menon, M., He, L., Abdurrob, F., Jiang, X., et al. (2019) · Nature · doi:10.1038/s41586-019-1195-2 · Cited by 2,568
Amyloid deposition as the central event in the aetiology of Alzheimer’s disease
Hardy, J., & Allsop, D. (1991) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(91)90609-v · Cited by 2,538
Stages of the Pathologic Process in Alzheimer Disease: Age Categories From 1 to 100 Years
Braak, H., Thal, D. R., Ghebremedhin, E., & Del Tredici, K. (2011) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318232a379 · Cited by 2,194
The Cellular Phase of Alzheimer’s Disease
De Strooper, B., & Karran, E. (2016) · Cell · doi:10.1016/j.cell.2015.12.056 · Cited by 1,990
Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease
Butterfield, D. A., & Halliwell, B. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0132-6 · Cited by 1,954 · cited 1×
“Oxidative and endoplasmic reticulum (ER) stress, prominent metabolic features (7, 8) of early AD (9, 10), are associated with reduced cerebral blood flow (CBF) (11) and with up-regulation of the sigma 1 receptor (S1R) in the ER (12, 13).”
BackgroundNeuroligins and neurexins link synaptic function to cognitive disease
Südhof, T. C. (2008) · Nature · doi:10.1038/nature07456 · Cited by 1,849 · cited 1×
“Synaptic loss begins early in the disease and progresses over the course of AD pathology (45).”
BackgroundScheltens, P., Leys, D., Barkhof, F., Huglo, D. G., Weinstein, H. C., Vermersch, P., Kuiper, M. A., Steinling, M., Wolters, E. C., & Valk, J. (1992) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.55.10.967 · Cited by 1,816
Oxidative Stress, Synaptic Dysfunction, and Alzheimer’s Disease
Tönnies, E., & Trushina, E. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-161088 · Cited by 1,750
Synaptic Energy Use and Supply
Harris, J. J., Jolivet, R., & Attwell, D. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.019 · Cited by 1,747
Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: Recent advances.
Wang, W., Zhao, F., Ma, X., Perry, G., & Zhu, X. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00376-6 · Cited by 1,274
Parametric Imaging of Ligand-Receptor Binding in PET Using a Simplified Reference Region Model
Gunn, R. N., Lammertsma, A. A., Hume, S. P., & Cunningham, V. J. (1997) · NeuroImage · doi:10.1006/nimg.1997.0303 · Cited by 1,085
Self-citationRole of oxidative stress in Alzheimer’s disease
HUANG, W.-J., ZHANG, X., & CHEN, W.-W. (2016) · Biomedical Reports · doi:10.3892/br.2016.630 · Cited by 1,023
Palmqvist, S., Schöll, M., Strandberg, O., Mattsson, N., Stomrud, E., Zetterberg, H., Blennow, K., Landau, S., Jagust, W., & Hansson, O. (2017) · Nature Communications · doi:10.1038/s41467-017-01150-x · Cited by 911
Mitochondria and Mitochondrial Cascades in Alzheimer’s disease
Swerdlow, R. H. (2018) · Journal of Alzheimer’s Disease · doi:10.3233/jad-170585 · Cited by 850
Scahill, R. I., Schott, J. M., Stevens, J., Rossor, M. N., & Fox, N. C. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.052587399 · Cited by 773
Müller‐Gärtner, H. W., Links, J. M., Prince, J. L., Bryan, R. N., McVeigh, E. R., Leal, J. P., Davatzikos, C. A., & Frost, J. J. (1992) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1992.81 · Cited by 756
Selective vulnerability in neurodegenerative diseases
Fu, H., Hardy, J., & Duff, K. E. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0221-2 · Cited by 585
A giant molecular proton pump: structure and mechanism of respiratory complex I
Sazanov, L. A. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3997 · Cited by 579
Imaging synaptic density in the living human brain
Finnema, S. J., Nabulsi, N. B., Eid, T., Detyniecki, K., Lin, S.-F., Chen, M.-K., Dhaher, R., Matuskey, D., Baum, E., Holden, D., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf6667 · Cited by 575
Ge, P., Dawson, V. L., & Dawson, T. M. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00367-7 · Cited by 496
Hedskog, L., Pinho, C. M., Filadi, R., Rönnbäck, A., Hertwig, L., Wiehager, B., Larssen, P., Gellhaar, S., Sandebring, A., Westerlund, M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1300677110 · Cited by 478
Imaging dopamine receptors in humans with [11C]-(+)-PHNO: Dissection of D3 signal and anatomy
Tziortzi, A. C., Searle, G. E., Tzimopoulou, S., Salinas, C. A., Beaver, J. D., Jenkinson, M., Laruelle, M. A., Rabiner, E. A., & Gunn, R. N. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.06.044 · Cited by 442
Self-citationMicroglia-Mediated Synapse Loss in Alzheimer's Disease
Rajendran, L., & Paolicelli, R. C. (2018) · The Journal of Neuroscience · doi:10.1523/jneurosci.1136-17.2017 · Cited by 355
The Sigma-1 Receptor as a Pluripotent Modulator in Living Systems
Su, T., Su, T., Nakamura, Y., & Tsai, S. (2016) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2016.01.003 · Cited by 332
In vivo measurement of widespread synaptic loss in Alzheimer’s disease with SV2A PET
Mecca, A. P., Chen, M., O'Dell, R. S., Naganawa, M., Toyonaga, T., Godek, T. A., Harris, J. E., Bartlett, H. H., Zhao, W., Nabulsi, N. B., et al. (2020) · Alzheimer's & Dementia · doi:10.1002/alz.12097 · Cited by 288
Role of sigma-1 receptors in neurodegenerative diseases
Nguyen, L., Lucke-Wold, B. P., Mookerjee, S. A., Cavendish, J. Z., Robson, M. J., Scandinaro, A. L., & Matsumoto, R. R. (2014) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2014.12.005 · Cited by 236
Binding properties of SA4503, a novel and selective σ1 receptor agonist
Matsuno, K., Nakazawa, M., Okamoto, K., Kawashima, Y., & Mita, S. (1996) · European Journal of Pharmacology · doi:10.1016/0014-2999(96)00201-4 · Cited by 189
Vascular oxidative stress in Alzheimer disease
Zhu, X., Smith, M. A., Honda, K., Aliev, G., Moreira, P. I., Nunomura, A., Casadesús, G., Harris, P. L. R., Siedlak, S. L., & Perry, G. L. (2007) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2007.01.039 · Cited by 175
Low density of sigma1 receptors in early Alzheimer’s disease
Mishina, M., Ohyama, M., Ishii, K., Kitamura, S., Kimura, Y., Oda, K.-I., Kawamura, K., Sasaki, T., Kobayashi, S., Katayama, Y., et al. (2008) · Annals of Nuclear Medicine · doi:10.1007/s12149-007-0094-z · Cited by 172
Wang, J., Shanmugam, A. K., Markand, S., Zorrilla, E. P., Ganapathy, V., & Smith, S. B. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.04.009 · Cited by 136
The Role of Sigma-1 Receptor, an Intracellular Chaperone in Neurodegenerative Diseases
Penke, B., Fülöp, L., Szűcs, M., & Frecska, E. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170529104323 · Cited by 132
Patterns of atrophy in pathologically confirmed dementias: a voxelwise analysis
Harper, L., Bouwman, F. H., Burton, E. J., Barkhof, F., Scheltens, P., O'Brien, J. T., Fox, N. C., Ridgway, G. R., & Schott, J. M. (2017) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2016-314978 · Cited by 131
Critical review: involvement of endoplasmic reticulum stress in the aetiology of Alzheimer's disease
Hashimoto, S., & Saido, T. C. (2018) · Open Biology · doi:10.1098/rsob.180024 · Cited by 129
Subramanian, J., Savage, J. C., & Tremblay, M. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.592607 · Cited by 127
σ1 and σ2 receptor binding affinity and selectivity of SA4503 and fluoroethyl SA4503
Lever, J. R., Gustafson, J. L., Xu, R., Allmon, R. L., & Lever, S. Z. (2006) · Synapse · doi:10.1002/syn.20253 · Cited by 108
Arterial spin labeling for the measurement of cerebral perfusion and angiography
Jezzard, P., Chappell, M. A., & Okell, T. W. (2017) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x17743240 · Cited by 106
In vivo evaluation of [11C]SA4503 as a PET ligand for mapping CNS sigma1 receptors
Kawamura, K., Ishiwata, K., Tajima, H., Ishii, S., Matsuno, K., Homma, Y., & Senda, M. (2000) · Nuclear Medicine and Biology · doi:10.1016/s0969-8051(00)00081-0 · Cited by 105
In Vivo Mitochondrial and Glycolytic Impairments in Patients with Alzheimer Disease
Terada, T., Obi, T., Bunai, T., Matsudaira, T., Yoshikawa, E., Ando, I., Futatsubashi, M., Tsukada, H., & Ouchi, Y. (2020) · Neurology · doi:10.1212/wnl.0000000000009249 · Cited by 103
Self-citationAβ-induced vulnerability propagates via the brain’s default mode network
Pascoal, T. A., Mathotaarachchi, S. S., Kang, M. S., Mohaddes, S., Shin, M., Park, A. Y., Parent, M. J., Benedet, A. L., Chamoun, M., Therriault, J., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10217-w · Cited by 90
Rojas, S., Herance, J. R., Gispert, J. D., Abad, S., Llongarriu, È. T., Jiménez, X., Pareto, D., Perpiñá, U., Sarroca, S., Rodrı́guez, E., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.12.027 · Cited by 88
Mansur, A., Rabiner, E. A., Comley, R. A., Lewis, Y. L., Middleton, L. T., Huiban, M., Passchier, J., Tsukada, H., & Gunn, R. N. (2019) · Journal of Nuclear Medicine · doi:10.2967/jnumed.119.228080 · Cited by 85
Self-citationTerada, T., Therriault, J., Kang, M. S., Savard, M., Pascoal, T. A., Lussier, F. Z., Tissot, C., Wang, Y.-T., Benedet, A. L., Matsudaira, T., et al. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00448-1 · Cited by 79
Self-citationHarada, N., Nishiyama, S., Kanazawa, M., & Tsukada, H. (2013) · Journal of Labelled Compounds and Radiopharmaceuticals · doi:10.1002/jlcr.3056 · Cited by 65
Self-citationMapping of human cerebral sigma1 receptors using positron emission tomography and [11C]SA4503
Sakata, M., Kimura, Y., Naganawa, M., Oda, K., Ishii, K., Chihara, K., & Ishiwata, K. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2006.11.055 · Cited by 61
Amyloid Load: A More Sensitive Biomarker for Amyloid Imaging
Whittington, A., & Gunn, R. N. (2018) · Journal of Nuclear Medicine · doi:10.2967/jnumed.118.210518 · Cited by 61
Self-citationShiba, K., Ogawa, K., Ishiwata, K., Yajima, K., & Mori, H. (2006) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2005.11.044 · Cited by 57
Onwordi, E. C., Whitehurst, T., Mansur, A., Statton, B., Berry, A., Quinlan, M., O’Regan, D. P., Rogdaki, M., Marques, T. R., Rabiner, E. A., et al. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01515-3 · Cited by 55
Self-citationTsukada, H., Ohba, H., Kanazawa, M., Kakiuchi, T., & Harada, N. (2013) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-013-2628-z · Cited by 40
Self-citationRamakrishnan, N. K., Visser, A. K. D., Schepers, M., Luurtsema, G., Nyakas, C. J., Elsinga, P. H., Ishiwata, K., Dierckx, R., & van Waarde, A. (2014) · Psychopharmacology · doi:10.1007/s00213-014-3533-2 · Cited by 36
Characterization of [3H]pentazocine binding sites in post-mortem human frontal cortex
Kornhuber, J., Schoppmeyer, K., Bendig, C., & Riederer, P. F. (1996) · Journal of Neural Transmission · doi:10.1007/bf01292615 · Cited by 32
SA4503: A Novel Sigma1Receptor Agonist
Matsuno, K., & Mita, S. (1998) · CNS Drug Reviews · doi:10.1111/j.1527-3458.1998.tb00038.x · Cited by 32
Mansur, A., Rabiner, E. A., Tsukada, H., Comley, R. A., Lewis, Y. L., Huiban, M., Passchier, J., & Gunn, R. N. (2020) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20928149 · Cited by 24
Self-citationAnalysis of Differential Expression of Synaptic Vesicle Protein 2A in the Adult Rat Brain
Mendoza-Torreblanca, J. G., García-Cruz, M. E., Sánchez-Cruz, I., Gomez-Gonzalez, B., Juárez-Méndez, S., & Gómez-Lira, G. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.09.004 · Cited by 18
Kazami, S., Nishiyama, S., Kimura, Y., Itoh, H., & Tsukada, H. (2018) · Mitochondrion · doi:10.1016/j.mito.2018.03.001 · Cited by 15
Self-citationEfange, S. M. N., von Hohenberg, K., Khare, A. B., Tu, Z., Mach, R. H., & Parsons, S. M. (2000) · Nuclear Medicine and Biology · doi:10.1016/s0969-8051(00)00157-8 · Cited by 14
Banister, S. D., Manoli, M., & Kassiou, M. (2013) · Journal of Labelled Compounds and Radiopharmaceuticals · doi:10.1002/jlcr.3010 · Cited by 12
Hirata, M., Mori, T., Soga, S., Umeda, T., & Ohmomo, Y. (2006) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.29.2009 · Cited by 7
Cited by
Sorted by citations
Targeting mitophagy in neurodegenerative diseases
Antico, O., Thompson, P. W., Hertz, N. T., Muqit, M. M. K., & Parton, L. E. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01105-0 · Cited by 187
Defining blood-induced microglia functions in neurodegeneration through multiomic profiling
Mendiola, A. S., Yan, Z., Dixit, K., Johnson, J. R., Bouhaddou, M., Meyer-Franke, A., Shin, M.-G., Yong, Y., Agrawal, A., MacDonald, E., et al. (2023) · Nature Immunology · doi:10.1038/s41590-023-01522-0 · Cited by 124
Wang, Z., Wang, C., Yuan, B., Liu, L., Zhang, H., Zhu, M., Chai, H., Peng, J., Huang, Y. H., Zhou, S., et al. (2025) · Microbiome · doi:10.1186/s40168-024-02001-w · Cited by 125
Tsartsalis, S., Sleven, H., Fancy, N., Wessely, F., Smith, A. M., Willumsen, N., Cheung, T. K. D., Rokicki, M. J., Chau, V., Ifie, E., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-46630-z · Cited by 95
Self-citationLista, S., Imbimbo, B. P., Grasso, M., Fidilio, A., Emanuele, E., Minoretti, P., López-Ortiz, S., Martín-Hernández, J., Gabelle, A., Caruso, G., et al. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03163-y · Cited by 81
Metadata
- Authors
- Venkataraman, A. V., Mansur, A., Rizzo, G., Bishop, C., Lewis, Y., Kocagoncu, E., Lingford-Hughes, A., Huiban, M., Passchier, J., Rowe, J. B., Tsukada, H., Brooks, D. J., Martarello, L., Comley, R. A., Chen, L., Schwarz, A. J., Hargreaves, R., Gunn, R. N., Rabiner, E. A., & Matthews, P. M.
- Affiliations
- UK Dementia Research Institute (GB)
- Invicro (United Kingdom) (GB)
- University of Cambridge, Cambridge CB2 2QQ, UK.
- Imperial College London (GB)
- Invicro LLC, London W12 0NN, UK.
- University of Cambridge (GB)
- Hamamatsu Photonics (Japan) (JP)
- Aarhus University (DK)
- Biogen (United States) (US)
- AbbVie (United States) (US)
- Pfizer (United States) (US)
- Takeda Pharmaceuticals Ltd, Cambridge, MA 02139, USA.
- Bristol-Myers Squibb (United States) (US)
- King's College London (GB)
- Corresponding author
- Matthews, Paul M.
- ORCID
- Venue
- Science Translational Medicine
- Published
- 2022-08-17
- Volume
- 14
- Issue
- 658
- Pages
- eabk1051-eabk1051
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- OpenAlex
- W4292266434
- Cited by
- 101
- References
- 64
- Citations by year
- 2026: 21 · 2025: 28 · 2024: 32 · 2023: 17 · 2022: 2
- FWCI
- 13.26
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Science Translational Medicine (publishedVersion)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Funders
- Alzheimer's Society
- National Institute for Health and Care Research (BRC1215-20014, NIHR-INF-0507, CL-2022-17-003)
- Department of Health and Social Care
- Imperial College London
- UK Dementia Research Institute
- Medical Research Council (MR/N029941/1, MR/L023784/2, SUAG/051 G101400, G101400, BRC-1215-20014, MR/T033371/1)
- NIHR Cambridge Biomedical Research Centre ((BRC-1215-20014))
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacological Receptor Mechanisms and Effects
- Keywords
- early Alzheimer's disease, endoplasmic reticulum stress, sigma-1 receptor, mitochondrial complex I, oxidative phosphorylation, mitochondrial dysfunction, SV2A, presynaptic dysfunction, brain atrophy, cerebral blood flow, disease progression, pharmacodynamic biomarkers, cognitive decline
- MeSH terms
- Alzheimer Disease, Brain, Cerebrovascular Circulation, Humans, Magnetic Resonance Imaging, Mitochondria, Biomarkers, Positron-Emission Tomography
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
