The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index; 1 of the 32 sources its claims cite were checked for support.
Retromer Stabilization Improves Cognitive Function and Synaptic Plasticity in a Mouse Model of Down Syndrome
Open accessAbstract
Background: Retromer complex proteins are decreased in postmortem brain tissues from Down syndrome subjects and inversely correlate with the Alzheimer’s disease-like neuropathology. However, whether targeting in vivo the retromer system affects cognitive deficits and synaptic function in Down syndrome remains unknown. Objective: The aim of the current study was to examine the effects of pharmacological retromer stabilization on cognitive and synaptic functions in a mouse model of Down syndrome. Methods: Ts65dn mice were administered the pharmacological chaperone, TPT-172, or vehicle from 4 to 9 months of age and then assessed for changes in cognitive function. To assess the effects of TPT-172 on synaptic plasticity, hippocampal slices from Ts65dn mice were incubated in TPT-172 and used for field potential recordings. Results: Chronic TPT-172 treatment improved performance in cognitive function tests, its incubation with hippocampal slices ameliorated synaptic function response. Conclusion: Pharmacological stabilization of the retromer complex improves synaptic plasticity and memory in a mouse model of Down syndrome. These results support the therapeutic potential of pharmacological retromer stabilization for individual with Down syndrome.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Chronic pharmacological stabilization of the retromer complex with TPT-172 improved some cognitive and synaptic measures in Ts65dn mice, a Down syndrome model. The study supports retromer stabilization as a potential therapeutic approach for cognitive decline in Down syndrome.
Key findings
- Ts65dn mice treated with TPT-172 from 4 to 9 months showed a significant increase in percent alternations in the Y-maze, with no difference in overall arm entries (n = 11 vehicle, 13 TPT; *p < 0.05).
- In fear conditioning, TPT-172-treated mice showed a significant increase in contextual recall freezing and a trend toward improvement in cued recall, with no baseline differences in training-phase freezing (*p < 0.05).
- Morris water maze performance did not differ significantly between groups, though trends toward improvement were reported in training and probe phases.
- In hippocampal slices from 9-month-old Ts65dn mice, acute TPT-172 incubation significantly increased paired-pulse facilitation at 25 and 100 ms inter-pulse intervals (n = 7 per group; *p < 0.05), while basal synaptic activity did not differ and early-phase LTP trended toward improvement.
Methods
- Ts65dn mice were oral gavaged 3 times weekly with 50 mg/kg TPT-172 or vehicle from 4 to 9 months of age; behavioral testing occurred between 8 and 9 months using Morris water maze, Y-maze, and fear conditioning.
- Hippocampal slices from 9-month-old Ts65dn mice were incubated in 25 μM TPT-172 or vehicle for 2 h, then field excitatory postsynaptic potentials were recorded from CA1 stratum radiatum via Schaffer collateral stimulation to assess input-output curves, short-term plasticity, and LTP.
- Data are expressed as mean ± SEM and analyzed with unpaired two-tailed Student t tests, with significance set at p < 0.05 using GraphPad Prism 9.00.
Limitations
- The authors state they do not have data showing TPT-172 crossed the blood-brain barrier in their mice, though they believe it does based on similarity to other small pharmacological chaperones.
- The authors state they did not investigate a possible effect of TPT-172 on neuropathology in this study, unlike prior work in an AD mouse model.
- The authors note that acute TPT-172 treatment did not significantly change basal synaptic activity or early LTP, and suggest treatment duration may matter, but additional studies are needed; evident from the text, several behavioral and electrophysiological outcomes were trends rather than significant, and sample sizes were modest (behavior n = 11–13; electrophysiology n = 7 per group).
Model-written summary. Check it against the paper before relying on it.
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Cites
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Claims the paper makes
1 of 32 cited sources checked · 1 supported · 0 flagged
- Premisecitation
Trisomy of chromosome 21 is one of the most significant risk factors for the development of early onset Alzheimer's disease.
“Trisomy of chromone 21 is one of the most significant risk factors for the development of early onset Alzheimer’s disease (AD) [1]”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [1] Wiseman, 2015, A genetic cause of Alzheimer disease: Mechanistic insights from Down syndrome, Nat Rev Neurosci source
- Findingown data
In the fear conditioning paradigm, there were no baseline differences in freezing response in the training phase between TPT-172-treated and vehicle-treated Ts65dn mice.
“In the fear conditioning paradigm, there were no baseline differences in freezing response in the training phase”
Quote in the paperNot a substantial claim- Rests on an assumption: The Ts65dn mouse model is a valid model of Down syndrome cognitive and synaptic deficits.
- Findingown data
In the Y-maze test, Ts65dn mice receiving TPT-172 had a significant increase in percent alternations compared to vehicle-treated mice.
“mice receiving TPT-172 had a significant increase in percent alternations (Fig. 1C).”
Quote in the paperSubstantial claim- Rests on an assumption: The Ts65dn mouse model is a valid model of Down syndrome cognitive and synaptic deficits.
- Findingown data
In the Y-maze test, Ts65dn mice receiving TPT-172 did not differ from vehicle-treated mice in the overall number of arm entries.
“In the Y-maze test, mice did not differ in the overall number of arm entries”
Quote in the paperNot a substantial claim - Findingown data
In the fear conditioning paradigm, TPT-172-treated Ts65dn mice had a significant increase in freezing response in the contextual recall test compared to vehicle-treated mice.
“but there was a significant increase of the freezing response in the contextual recall test”
Quote in the paperSubstantial claim- Rests on an assumption: The Ts65dn mouse model is a valid model of Down syndrome cognitive and synaptic deficits.
- Findingown data
The early-phase LTP response in hippocampal slices from Ts65dn mice incubated with TPT-172 was trending toward improvement compared to vehicle.
“however, the early-phase LTP response was trending toward improvement (Fig. 2C)”
- Also stated in: § DISCUSSION · hedged
“showed insignificant trends toward improvement in the early phase of LTP”
Quote in the paperNot a substantial claim- Rests on an assumption: The Ts65dn mouse model is a valid model of Down syndrome cognitive and synaptic deficits.
- Also stated in: § DISCUSSION · hedged
- Findingown data
Acute TPT-172 incubation significantly enhanced short-term plasticity (paired-pulse facilitation at 25 and 100 ms inter-pulse intervals) in hippocampal slices from Ts65dn mice.
“we saw a significant increase in paired-pulse facilitation (STP) at 25 and 100 ms inter-pulse intervals in hippocampal slices that were incubated with TPT-172 (Fig. 2B).”
- Also stated in: § DISCUSSION · plain
“Acute TPT-172 treatment significantly enhanced short-term plasticity”
Quote in the paperSubstantial claim- Rests on an assumption: The Ts65dn mouse model is a valid model of Down syndrome cognitive and synaptic deficits.
- Rests on an assumption: The cognitive and synaptic improvements produced by TPT-172 are due to stabilization of the retromer complex rather than off-target effects.
- Also stated in: § DISCUSSION · plain
- Findingown data
Basal synaptic activity did not differ between vehicle- and TPT-172-incubated hippocampal slices from 9-month-old Ts65dn mice.
“Basal synaptic activity did not differ between groups (Fig. 2A);”
- Also stated in: § DISCUSSION · plain
“acute hippocampal slice treatment with TPT-172 did not show any changes in basal synaptic activity”
Quote in the paperNot a substantial claim- Rests on an assumption: The Ts65dn mouse model is a valid model of Down syndrome cognitive and synaptic deficits.
- Also stated in: § DISCUSSION · plain
- Findingown data
In the fear conditioning paradigm, TPT-172-treated Ts65dn mice showed a trend toward improvement in cued recall compared to vehicle-treated mice.
“and a trend toward improvement in the cued recall in mice administered TPT-172 (Fig. 1E).”
Quote in the paperNot a substantial claim- Rests on an assumption: The Ts65dn mouse model is a valid model of Down syndrome cognitive and synaptic deficits.
- Premisecitation
Retromer complex proteins are decreased in postmortem brain tissues from Down syndrome subjects.
“Retromer complex proteins are decreased in postmortem brain tissues from Down syndrome subjects and inversely correlate with the Alzheimer’s disease-like neuropathology.”
- Also stated in: § INTRODUCTION · boosted
“We previously showed that the retromer complex proteins are also reduced in postmortem brain tissues and induced pluripotent stem cell (iPSC) derived neurons from subjects with DS [9, 10].”
Quote in the paperSubstantial claim0 of 2 sources checked - Also stated in: § INTRODUCTION · boosted
- Premisecitation
The retromer's actions in the recycling pathway towards the cell membrane can facilitate synaptic plasticity by transporting glutamate receptors to the synapse.
“Furthermore, the retromer’s actions in the recycling pathway towards the cell membrane can facilitate synaptic plasticity by transporting glutamate receptors to the synapse [4, 14, 15].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [4] Vagnozzi, 2019, Endosomal sorting and trafficking, the retromer complex and neurodegeneration, Mol Psychiatry source
- cites [14] Qureshi, 2020, Endosomal trafficking in Alzheimer’s disease, Parkinson’s disease, and neuronal ceroid lipofuscinosis, Mol Cell Biol source
- cites [15] Li, 2016, Role of the retromer complex in neurodegenerative diseases, Front Aging Neurosci source
- Premisecitation
Ts65dn mice develop significant aging-related cognitive and neuropathological changes after 4 months of age.
“a time just prior to significant development of aging related cognitive and neuropathological changes in this model [17].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17] Hamlett, 2016, Cognitive impairment, neuroimaging, and Alzheimer’s neuropathology in mouse models of Down syndrome, Curr Alzheimer Res source
- Premisecitation
In vitro enhancement of retromer complex function significantly reduces classical Alzheimer's disease-like pathology measures in Down syndrome iPSC-derived neurons.
“Furthermore, we demonstrated that in vitro enhancement of retromer complex function significantly reduces classical AD-like pathology measures in DS iPSC-derived neurons [9].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [9] Curtis, 2022, Dysfunction of the retromer complex system contributes to amyloid and tau pathology in a stem cell model of Down syndrome, Alzheimers Dement (N Y) source
- Premisecitation
The retromer complex regulates post-synaptic trafficking of AMPA receptors.
“and post-synaptic trafficking of AMPA receptors [23].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [23] Temkin, 2017, The retromer supports AMPA receptor trafficking during LTP, Neuron source
- Premisecitation
The retromer complex regulates synaptic function through the recycling of synaptic proteins.
“aligning with the role of the retromer complex in regulating synaptic function through the recycling of synaptic proteins [20, 21].”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
TPT-172 was previously shown to be effective in reducing in vivo classical Alzheimer's disease-like neuropathology in mice.
“Additionally, the same drug was previously shown to be effective in reducing in vivo the classical AD-like neuropathology in mice.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [7] Li, 2023, Beneficial effect of a small pharmacologic chaperone on the established Alzheimer’s disease phenotype, J Alzheimers Dis source
- cites [8] Li, 2020, A pharmacological chaperone improves memory by reducing Abeta and tau neuropathology in a mouse model with plaques and tangles, Mol Neurodegener source
- Premisecitation
Retromer complex protein levels inversely correlate with Alzheimer's disease-like neuropathology in Down syndrome subjects.
“Retromer complex proteins are decreased in postmortem brain tissues from Down syndrome subjects and inversely correlate with the Alzheimer’s disease-like neuropathology.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Retromer complex proteins are reduced in induced pluripotent stem cell (iPSC)-derived neurons from subjects with Down syndrome.
“We previously showed that the retromer complex proteins are also reduced in postmortem brain tissues and induced pluripotent stem cell (iPSC) derived neurons from subjects with DS [9, 10].”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationown data
These results support the therapeutic potential of pharmacological retromer stabilization for individuals with Down syndrome.
“These results support the therapeutic potential of pharmacological retromer stabilization for individual with Down syndrome.”
- Also stated in: § DISCUSSION · plain
“Our study provides further support for the role of pharmacological stabilization of the retromer complex as a viable therapeutic approach against cognitive decline in DS subjects.”
Quote in the paperSubstantial claim- Rests on an assumption: Retromer complex dysfunction contributes to cognitive and synaptic deficits in Down syndrome.
- Rests on an assumption: The Ts65dn mouse model is a valid model of Down syndrome cognitive and synaptic deficits.
- Rests on an assumption: The cognitive and synaptic improvements produced by TPT-172 are due to stabilization of the retromer complex rather than off-target effects.
- Also stated in: § DISCUSSION · plain
- Interpretationown data
Chronic administration of TPT-172 improved cognitive impairments in Ts65dn mice.
“Thus, overall, chronic administration of TPT-172 improved cognitive impairments in Ts65dn mice.”
- Also stated in: § Results: · plain
“Chronic TPT-172 treatment improved performance in cognitive function tests”
Quote in the paperSubstantial claim- Rests on an assumption: The Ts65dn mouse model is a valid model of Down syndrome cognitive and synaptic deficits.
- Rests on an assumption: The cognitive and synaptic improvements produced by TPT-172 are due to stabilization of the retromer complex rather than off-target effects.
- Also stated in: § Results: · plain
- Interpretationcitation
TPT-172 crosses the blood-brain barrier in mice, inferred from similarity to other small pharmacological chaperones.
“Although we do not have data showing that the pharmacological chaperone we used in our study has crossed the blood-brain barrier in our mice, we are confident that this is the case based on the similarity with other small pharmacological chaperones, most of which are predicted to have a good brain permeability [18, 19].”
Quote in the paperSubstantial claim0 of 2 sources checked
- It may state two separate claims as one. 5
- Probably not a substantial claim. 8
It may state two separate claims as one.
Findingown dataIn the Morris water maze test, there were no significant differences between TPT-172-treated and vehicle-treated Ts65dn mice, though there were trends toward improvement in both the training and probe phases in the TPT-172 group.
“No significant differences were observed in the MWM test between the two groups, though there were trends toward improvement in both the training and probe phases in mice receiving TPT-172 (Fig. 1D).”
Quote in the paperNot a substantial claim- Rests on an assumption: The Ts65dn mouse model is a valid model of Down syndrome cognitive and synaptic deficits.
It may state two separate claims as one.
Findingown dataTs65dn mice treated with TPT-172 from 4 to 9 months show no significant changes in general health, weight, or survival compared to vehicle-treated mice.
“No significant changes in general health, weight, or survival were detected between mice receiving vehicle or TPT-172 (Fig. 1A, B).”
Quote in the paperNot a substantial claimProbably not a substantial claim.
PremisecitationThe endo-lysosomal network is a key biological pathway central to Alzheimer's disease pathogenesis.
“In recent years, genetic and functional studies have highlighted the endo-lysosomal network as a key biological pathway central to AD pathogenesis [3–5].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [3] Karch, 2015, Alzheimer’s disease risk genes and mechanisms of disease pathogenesis, Biol Psychiatry source
- cites [4] Vagnozzi, 2019, Endosomal sorting and trafficking, the retromer complex and neurodegeneration, Mol Psychiatry source
- cites [5] Wong, 2020, Endosomal-lysosomal processing of neurodegeneration-associated proteins in astrocytes, Int J Mol Sci source
Probably not a substantial claim.
PremisecitationDysfunction of the retromer complex, secondary to decreases in VPS35 and VPS26 proteins, has been reported in brains of human patients with Alzheimer's disease.
“Dysfunction of the retromer complex, secondary to decreases in VPS35 and VPS26 proteins, has been reported brains of human patients with AD [6]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6] Wang, 2014, Dysregulation of protein trafficking in neurodegeneration, Mol Neurodegener source
It may state two separate claims as one.
PremisecitationTPT-172 stabilizes the retromer complex by increasing stability of the VPS35-VPS29 binding domain and protecting the VPS35-VPS26-VPS29 recognition core from denaturation.
“TPT-172, which is known to stabilize the retromer complex protein [9]. Thus, this molecule enhances retromer complex function by increasing stability of the VPS35-VPS29 binding domain, the weakest link of the VPS35-VPS26-VPS29 heterotrimer, and consequently protecting the recognition core from denaturation [9,16].”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationThe retromer complex regulates pre-synaptic vesicle release.
“recent studies which have demonstrated the role of the retromer complex system in the regulation of pre-synaptic vesicle release [22, 23]”
Quote in the paperNot a substantial claim0 of 2 sources checkedIt may state two separate claims as one.
PremisecitationPeople with Down syndrome develop the neuropathological hallmarks of Alzheimer's disease and severe cognitive decline by age 40.
“people with DS develop the neuropathological hallmarks of AD and severe cognitive decline by age 40 [2].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [2] Head, 2012, Alzheimer’s disease in Down syndrome, Eur J Neurodegener Dis
Probably not a substantial claim.
PremisecitationEnhancing retromer function influences both amyloid and tau neuropathology in models of Alzheimer's disease.
“enhancing retromer function has been shown to influence both amyloid and tau neuropathology in models of the disease [7, 8].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [7] Li, 2023, Beneficial effect of a small pharmacologic chaperone on the established Alzheimer’s disease phenotype, J Alzheimers Dis source
- cites [8] Li, 2020, A pharmacological chaperone improves memory by reducing Abeta and tau neuropathology in a mouse model with plaques and tangles, Mol Neurodegener source
It may state two separate claims as one.
Interpretationown dataPharmacological stabilization of the retromer complex improves synaptic plasticity and memory in a mouse model of Down syndrome.
“Pharmacological stabilization of the retromer complex improves synaptic plasticity and memory in a mouse model of Down syndrome.”
- Also stated in: § INTRODUCTION · plain
“Herein we report that stabilization of the retromer complex by a small pharmacological chaperone results in improved cognition and synaptic function in DS mice.”
- Also stated in: § DISCUSSION · boosted
“Our study shows that pharmacological stabilization of the retromer complex system results in an amelioration of cognitive function and synaptic plasticity in a mouse model of DS.”
Quote in the paperSubstantial claim- Rests on an assumption: Retromer complex dysfunction contributes to cognitive and synaptic deficits in Down syndrome.
- Rests on an assumption: The Ts65dn mouse model is a valid model of Down syndrome cognitive and synaptic deficits.
- Rests on an assumption: The cognitive and synaptic improvements produced by TPT-172 are due to stabilization of the retromer complex rather than off-target effects.
- Also stated in: § INTRODUCTION · plain
Probably not a substantial claim. The paper’s conclusions may not depend on it.
InterpretationcitationOur current results agree with previous studies in which TPT-172 was chronically administered to a mouse model of Alzheimer's disease with amyloid plaques and tangles (3xTg mice).
“Thus, our current results agree with our previous studies in which TPT-172 was chronically administered to a mouse model of AD with amyloid plaques and tangles, the 3xTg mice [7, 8].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [7] Li, 2023, Beneficial effect of a small pharmacologic chaperone on the established Alzheimer’s disease phenotype, J Alzheimers Dis source
- cites [8] Li, 2020, A pharmacological chaperone improves memory by reducing Abeta and tau neuropathology in a mouse model with plaques and tangles, Mol Neurodegener source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductnone givenMice were monitored for changes in weight, health, and signs of toxicity.
“Mice were monitored for changes in weight, health, and signs of toxicity.”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductnone givenAll animal care and procedures were approved by the Institutional Animal Care and Usage Committee in accordance with US National Institutes of Health guidelines.
“All animal care and procedures were approved by the Institutional Animal Care and Usage Committee in accordance with the US National Institutes of Health guidelines.”
Quote in the paperNot a substantial claimProbably not a substantial claim.
Study design and conductnone givenBoth control and TPT-172 treated slices from each animal were used for field potential recordings.
“Both control and TPT-172 treated slices from each animal were used for field potential recordings.”
Quote in the paperSubstantial claim
The paper relies on this without support.
Whether targeting the retromer system in vivo affects cognitive deficits and synaptic function in Down syndrome was unknown before this study.
“However, whether targeting in vivo the retromer system affects cognitive deficits and synaptic function in Down syndrome remains unknown.”
The paper relies on this without support.
Retromer complex dysfunction contributes to cognitive and synaptic deficits in Down syndrome.
“Retromer complex proteins are decreased in postmortem brain tissues from Down syndrome subjects and inversely correlate with the Alzheimer’s disease-like neuropathology.”
The paper relies on this without support.
The Ts65dn mouse model is a valid model of Down syndrome cognitive and synaptic deficits.
“To expand upon our previous findings, in the current study we utilize the Ts65dn mouse model of DS to examine the biological effects of chronic in vivo retromer stabilization on memory and synaptic function.”
The paper relies on this without support.
The cognitive and synaptic improvements produced by TPT-172 are due to stabilization of the retromer complex rather than off-target effects.
“To increase retromer function in Ts65dn mice, we utilized a small molecule pharmacological chaperone, TPT-172, which is known to stabilize the retromer complex protein [9].”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
LTP stimulation intervals differ between methods and figure caption
MinorThe methods specify 60-second intervals between tetanic pulses, whereas the Fig. 2 caption specifies 20-second intervals.
“Three consecutive tetanic pulses of 1-s duration and 100 Hz were applied at 60-s inter-pulse intervals to induce LTP.”
“C) LTP induced with 3 consecutive 1-s high-frequency stimulation pulses of 100 Hz at a 20-s inter-pulse interval.”
Paired-pulse ratio is defined in opposite directions
MinorThe methods define paired-pulse facilitation as the slope at pulse 2 divided by the slope at pulse 1, but the Fig. 2 caption defines it as pulse 1 divided by pulse 2.
“The ratio of the fEPSP slope at pulse 2 to the fEPSP slope at pulse 1 was determined using respective inter-pulse interval time points.”
“B) Time dependence of paired-pulse facilitation of the fEPSP slope, presented as a ratio of the fEPSP slope at pulse 1 to the fEPSP slope at pulse 2, for different time-points.”
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Metadata
- Authors
- Curtis, M. E., Smith, T., Nenov, M., Blass, B. E., & Praticò, D.
- Affiliations
- Temple University (US)
- Corresponding author
- Praticò, Domenico
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2023-07-18
- Volume
- 94
- Issue
- 2
- Pages
- 513-518
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC10357169
- OpenAlex
- W4380632208
- Cited by
- 3
- References
- 23
- Citations by year
- 2025: 2 · 2024: 1
- FWCI
- 0.67
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Alzheimer s Disease (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- retromer complex, Down syndrome
- MeSH terms
- Alzheimer Disease, Animals, Cognition, Disease Models, Animal, Down Syndrome, Hippocampus, Mice, Transgenic, Neuronal Plasticity, Mice
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.
A language model drew the claims from the paper on 2026-11-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
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 ›
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