The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index; none of the 32 sources its claims cite is checked for support yet.
Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease
Open accessAbstract
Importance: It is critically important to improve our ability to diagnose and track Alzheimer disease (AD) as early as possible. Individuals with autosomal dominant forms of AD can provide clues as to which and when biological changes are reliably present prior to the onset of clinical symptoms. Objective: To characterize the associations between amyloid and tau deposits in the brains of cognitively unimpaired and impaired carriers of presenilin 1 (PSEN1) E280A mutation. Design, Setting, and Participants: In this cross-sectional imaging study, we leveraged data from a homogeneous autosomal dominant AD kindred, which allowed us to examine measurable tau deposition as a function of individuals' proximity to the expected onset of dementia. Cross-sectional measures of carbon 11-labeled Pittsburgh Compound B positron emission tomography (PET) and flortaucipir F 18 (previously known as AV 1451, T807) PET imaging were assessed in 24 PSEN1 E280A kindred members (age range, 28-55 years), including 12 carriers, 9 of whom were cognitively unimpaired and 3 of whom had mild cognitive impairment, and 12 cognitively unimpaired noncarriers. Main Outcomes and Measures: We compared carbon 11-labeled Pittsburgh Compound B PET cerebral with cerebellar distribution volume ratios as well as flortaucipir F 18 PET cerebral with cerebellar standardized uptake value ratios in mutation carriers and noncarriers. Spearman correlations characterized the associations between age and mean cortical Pittsburgh Compound B distribution volume ratio levels or regional flortaucipir standardized uptake value ratio levels in both groups. Results: Of the 24 individuals, the mean (SD) age was 38.0 (7.4) years, or approximately 6 years younger than the expected onset of clinical symptoms in carriers. Compared with noncarriers, cognitively unimpaired mutation carriers had elevated mean cortical Pittsburgh Compound B distribution volume ratio levels in their late 20s, and 7 of 9 carriers older than 30 years reached the threshold for amyloidosis (distribution volume ratio level > 1.2). Elevated levels of tau deposition were seen within medial temporal lobe regions in amyloid-positive mutation carriers 6 years before clinical onset of AD in this kindred. Substantial tau deposition in the neocortex was only observed in 1 unimpaired carrier and in those with mild cognitive impairment. β-Amyloid uptake levels were diffusely elevated in unimpaired carriers approximately 15 years prior to expected onset of mild cognitive impairment. In carriers, higher levels of tau deposition were associated with worse performance on the Mini-Mental State Examination (entorhinal cortex: r = -0.60; P = .04; inferior temporal lobe: r = -0.54; P = .06) and the Consortium to Establish a Registry for Alzheimer Disease Word List Delayed Recall (entorhinal cortex: r = -0.86; P < .001; inferior temporal lobe: r = -0.70; P = .01). Conclusions and Relevance: The present findings add to the growing evidence that molecular markers can characterize biological changes associated with AD in individuals who are still cognitively unimpaired. The findings also suggest that tau PET imaging may be useful as a biomarker to distinguish individuals at high risk to develop the clinical symptoms of AD and to track disease progression.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“followed by unimpaired mutation carriers (mean [SD], 1.21 [0.14]; 95% CI, -0.24 to -0.08)”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Carbon 11-Labeled PiB DVR in PSEN1 Mutation Carriers
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
None of the sources cited for this claim have been checked yet.
In the paper
“β-Amyloid uptake levels were diffusely elevated in unimpaired carriers approximately 15 years prior to expected onset of MCI, consistent with our previous report 29 of increased mean cortical 18F florbetapir SUVR levels in individuals from the same kindred.”
- Also stated in: § Downloaded From: https://jamanetwork.com/ on 07/13/2023 · hedged
“This result is consistent with the present study and another one based on the Colombian kindred, 6 both of which showed that PiB levels begin to be elevated approximately 15 years prior to estimated onset of MCI.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Downloaded From: https://jamanetwork.com/ on 07/13/2023
What the sources say
- Not checked yetcites [29] 29. Sepulveda-Falla D, Matschke J, Bernreuther C, et al. Deposition of hyperphosphorylated tau in cerebellum of PS1 E280A Alzheimer's disease. Brain Pathol. 2011;21(4):452-463.
- Not checked yetcites [6] 6. Fleisher AS, Chen K, Quiroz YT, et al. Associations between biomarkers and age in the presenilin 1 E280A autosomal dominant Alzheimer disease kindred: a cross-sectional study. JAMA Neurol. 2015;72(3):316-324.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Downloaded From: https://jamanetwork.com/ on 07/13/2023 · hedged
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“who in turn showed higher carbon 11-labeled PiB DVR than noncarriers (mean [SD], 1.04 [0.02]; P < .001).”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Carbon 11-Labeled PiB DVR in PSEN1 Mutation Carriers
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and the Consortium to Establish a Registry for Alzheimer Disease Word List Delayed Recall (entorhinal cortex: r = -0.86;P < .001;inferior temporal lobe: r = -0.70;P = .01).”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“hippocampus (mean [SD] SUVR, 1.37 [0.30] vs 1.12 [0.08]; mean difference, -0.25; 95% CI, -0.49 to -0.03; P = .03)”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Regional 18F FTP Binding in PSEN1 Mutation Carriers
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Inferior temporal lobe 18F FTP binding was associated with higher mean cortical PiB retention in mutation carriers (r = 0.67; P = .02).”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > 18F FTP and PiB Binding in Relation to Each Other
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Furthermore, 18F FTP SUVR levels were correlated with clinical measures.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Downloaded From: https://jamanetwork.com/ on 07/13/2023
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Compared with noncarriers, cognitively unimpaired mutation carriers had elevated mean cortical Pittsburgh Compound B distribution volume ratio levels in their late 20s”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In mutation carriers, greater age was associated with both higher cortical PiB DVR (r = 0.88; P < .001)”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Associations Among PET Measures, Age, and Cognitive Measures
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Individual threshold-based anatomic assessments showed that unimpaired carriers with the highest PiB DVR values also had the highest FTP binding in the medial temporal lobe and inferior temporal regions.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Regional 18F FTP Binding in PSEN1 Mutation Carriers
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
- It may state two separate claims as one. 14
- Probably not a substantial claim. 16
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The youngest mutation carrier, aged 28 years, showed no PIB elevation (PiB = 1.02)”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Carbon 11-Labeled PiB DVR in PSEN1 Mutation Carriers
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No elevated amyloid accumulation was seen in any noncarriers, as expected (PiB DVR < 1.1 in all individuals).”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Carbon 11-Labeled PiB DVR in PSEN1 Mutation Carriers
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Compared with unimpaired mutation carriers, cognitively impaired mutation carriers were older and had significantly lower neuropsychological test scores.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Demographic Information
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“but beginning at age 29 years, mutation carriers showed elevated PiB uptake (PiB DVR > 1.1 in all but 1 individual).”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Carbon 11-Labeled PiB DVR in PSEN1 Mutation Carriers
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Additionally, the study of tau PET in combination with Pittsburgh Compound B (PiB) PET measures can reveal the extent to which amyloidtau relations in ADAD differ from those seen in sporadic AD.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All data were acquired by investigators who were masked to the participants' genetic status.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Study Design and Participants
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Presenilin 1 (PSEN1; OMIM, 104311) mutations predispose individuals to develop autosomal dominant Alzheimer disease (ADAD), usually relatively early in adulthood.5”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Abstract
What the sources say
- Not checked yetcites [5] 5. Lopera F, Ardilla A, Martínez A, et al. Clinical features of early-onset Alzheimer disease in a large kindred with an E280A presenilin-1 mutation. JAMA. 1997;277(10):793-799.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Positron emission tomography data were not partial volume corrected.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Image Acquisition and Processing
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The cognitively unimpaired mutation carrier and noncarrier groups did not differ significantly in their age, sex, education, or neuropsycho-logical test scores.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Demographic Information
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A lzheimer disease (AD) is defined at the neuropathological molecular level by amyloid plaques and neurofibrillary tangles.1,2”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Abstract
What the sources say
- Not checked yetcites [1] 1. Iqbal K, Grundke-Iqbal I. Neurofibrillary pathology leads to synaptic loss and not the other way around in Alzheimer disease. J Alzheimers Dis. 2002;4(3):235-238.
- Not checked yetcites [2] 2. Crews L, Masliah E. Molecular mechanisms of neurodegeneration in Alzheimer's disease. Hum Mol Genet. 2010;19(R1):R12-R20.
Strength:plain· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
In the paper
“Approximately 30% of living mutation carriers from this kindred are currently experiencing symptoms of AD, with median ages of 44 years (95% CI, 43-45) at onset of mild cognitive impairment (MCI) and 49 years (49-50) at onset of dementia.9”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Abstract
What the sources say
- Not checked yetcites [9] 9. Acosta-Baena N, Sepulveda-Falla D, Lopera-Gómez CM, et al. Pre-dementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer's disease: a retrospective cohort study. Lancet Neurol. 2011;10(3):213-220.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This neuropathology generally follows a characteristic spatial distribution, with amyloid plaques beginning in neocortical association regions and tangles beginning in the medial temporal lobe and then spreading into adjacent association cortices with subsequent pancortical extension.3,4”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Abstract
What the sources say
- Not checked yetcites [3] 3. Arnold SE, Hyman BT, Flory J, Damasio AR, Van Hoesen GW. The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer's disease. Cereb Cortex. 1991;1(1):103-116.
- Not checked yetcites [4] 4. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991; 82(4):239-259.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Residing in Antioquia, Colombia, this kindred is estimated to have approximately 5000 living members, including approximately 1800 mutation carriers.9”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Abstract
What the sources say
- Not checked yetcites [9] 9. Acosta-Baena N, Sepulveda-Falla D, Lopera-Gómez CM, et al. Pre-dementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer's disease: a retrospective cohort study. Lancet Neurol. 2011;10(3):213-220.
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The findings also suggest that tau PET imaging may be useful as a biomarker to distinguish individuals at high risk to develop the clinical symptoms of AD and to track disease progression.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Rests on an assumption: Cross-sectional differences by age reflect the temporal sequence of tau and amyloid accumulation.
In the paper
“Flortaucipir F 18 was prepared at Massachusetts General Hospital with a mean (SD) radiochemical yield of 14% (3%) and a mean (SD) specific activity of 216 (60) GBq/μmol at the end of synthesis (60 min) and was validated for human use.16”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Image Acquisition and Processing
What the sources say
- Not checked yetcites [16] 16. Shoup TM, Yokell DL, Rice PA, et al. A concise radiosynthesis of the tau radiopharmaceutical, [(18)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Positron emission tomography images were reconstructed and attenuation-corrected, and each frame was evaluated to verify adequate count statistics and absence of head motion.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Image Acquisition and Processing
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Cognitively unimpaired mutation carriers and noncarriers were matched for sex, age, and education.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Study Design and Participants
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Results with white matter were very similar to the results using the cerebellum (eg, the statistical differences observed with cerebellum as the reference region were also observed with white matter as the reference).”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Carbon 11-Labeled PiB DVR in PSEN1 Mutation Carriers
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“To account for possible 18F FTP off-target binding in choroid plexus, which may confound hippocampal signal, we used a linear regression to regress the choroid plexus, as previously reported.21”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Image Acquisition and Processing
What the sources say
- Not checked yetcites [21] 21. Chien DT, Bahri S, Szardenings AK, et al. Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J Alzheimers Dis. 2013;34 (2):457-468.
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“While the pathogenesis of ADAD may be different from late-onset AD (LOAD) and some clinical features may differ, these conditions are markedly similar in terms of their biological profiles, including abnormalities in amyloid biomarkers, brain structure, and brain activity.6”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Abstract
What the sources say
- Not checked yetcites [6] 6. Fleisher AS, Chen K, Quiroz YT, et al. Associations between biomarkers and age in the presenilin 1 E280A autosomal dominant Alzheimer disease kindred: a cross-sectional study. JAMA Neurol. 2015;72(3):316-324.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“They also suggest that tau PET imaging may be useful as a biomarker to distinguish individuals at high risk to develop the clinical symptomatology of AD, track progression of the disease, and evaluate response to disease-modifying treatments.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Because age is predictive of clinical onset in the PSEN1 E280A mutation kindred, cross-sectional assessments across a wide age range in this well-defined cohort are perhaps analogous to what might be expected from the assessment of longitudinal trajectories of biomarker change.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Limitations
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Rests on an assumption: Age is predictive of clinical onset in the PSEN1 E280A mutation kindred.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, the present results are based on a relatively small sample size compared with studies of LOAD.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Limitations
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“These findings will inform ongoing preclinical trials with ADAD, such as the Alzheimer Prevention Initiative treatment trial of an Aβ-modifying agent.35”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Conclusions
What the sources say
- Not checked yetcites [35] 35. Benzinger T, Friedrichsen K, Sul Y, et al. Patterns of tau deposition using [18F]-AV-1451 in autosomal dominant Alzheimer's disease: results from the DIAN. Paper presented at: Human Amyloid Imaging 2016; January 14, 2016; Miami, FL.
Strength:plain· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, the results from the Colombia kindred agree with those from DIAN for both FTP and PiB imaging.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Downloaded From: https://jamanetwork.com/ on 07/13/2023
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As such, the temporal differences observed between amyloid and tau pathology in this study may be explained in part by limited detection of pathology by PET methods.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Limitations
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Most importantly, there is uncertainty regarding the extent to which the findings will generalize to LOAD and to other AD-causing mutations.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Limitations
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Tau imaging had not been extensively tested in autosomal dominant Alzheimer disease before this study.
“To our knowledge, tau imaging has not been extensively tested in ADAD to date.”
The paper relies on this without support.
Flortaucipir F 18 selectively binds tau aggregates.
“flortaucipir F 18 (18F FTP; previously known as AV 1451, T807), which selectively binds tau aggregates”
The paper relies on this without support.
Carbon 11-labeled PiB selectively binds amyloid deposits.
“carbon 11labeled PiB, which selectively binds amyloid deposits”
The paper relies on this without support.
Tau PET imaging holds promise for detecting Alzheimer disease in the preclinical stage.
“This novel biomarker holds promise for detecting AD in the preclinical stage.”
The paper relies on this without support.
Cross-sectional differences by age reflect the temporal sequence of tau and amyloid accumulation.
“In this study, we characterized the spatial pattern and temporal lag cross-sectionally of tau and amyloid deposition in the brains of 24 PSEN1 E280A mutation carriers and noncarriers from the largest known kindred with ADAD.”
The paper relies on this without support.
PSEN1 mutation carriers will go on to develop Alzheimer disease with virtual certainty.
“Studies of PSEN1 mutation carriers allow us to examine cognitively unimpaired individuals who will go on to develop AD in the future with virtual certainty.”
The paper relies on this without support.
Age is predictive of clinical onset in the PSEN1 E280A mutation kindred.
“Because age is predictive of clinical onset in the PSEN1 E280A mutation kindred, cross-sectional assessments across a wide age range in this well-defined cohort are perhaps analogous to what might be expected from the assessment of longitudinal trajectories of biomarker change.”
The paper relies on this without support.
The present study is the first to investigate tau aggregation using PET imaging in this kindred.
“To our knowledge, the present study is the first to investigate tau aggregation using PET imaging in this kindred.”
The paper relies on this without support.
The present sample represents one of the largest of its kind with amyloid and tau PET data in carriers of a single ADAD mutation.
“However, because of the rarity of these mutations, the present sample represents, to our knowledge, one of the largest of its kind with amyloid and tau PET data in carriers of a single ADAD mutation.”
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The cited source says what the claim attributes to it.
In the citing paper
“The reported patient was protected from the clinical effects of PSEN1-E280A, a highly penetrant mutation causing EOAD dementia41,42, for 28 years by the homozygous APOE3-R136S mutation36.”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [41]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“However, he had relatively limited Tau pathology in the entorhinal cortex (ERC) (SUVR = 1.34; Fig. 1a,c) and in other neocortical regions, such as the posterior cingulate cortex (PCC) and precuneus (SUVR PCC = 1.51; SUVR precuneus = 1.49; Fig. 1a)”
From Resilience to autosomal dominant Alzheimer’s disease in a Reelin-COLBOS heterozygous man (2023) · cites this paper as [3]
Experimental — accuracy not yet measuredIn the citing paper
“In contrast, the more appropriate longitudinal measures indicate that soluble tau phosphorylation occupancy decreases during the time of tau increase25, at least in DIAD, demonstrating an inverse correlation.”
From A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease (2020) · cites this paper as [25]
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.
Inferior-temporal cognition correlation has two P values
MinorThe abstract reports P = .06 for the inferior-temporal correlation with Mini-Mental State Examination performance, while the figure labels the same correlation, with the same r value, P = .07.
“inferior temporal lobe: r = -0.54;P = .06”
“FTP SUVR (Inferior-Temporal) r = -0.54P = .07”
Citations
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123
Albert, M. S., DeKosky, S. T., Dickson, D., Dubois, B., Feldman, H. H., Fox, N. C., Gamst, A., Holtzman, D. M., Jagust, W. J., Petersen, R. C., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.008 · Cited by 10,152
Jack, C. R., Knopman, D. S., Jagust, W. J., Petersen, R. C., Weiner, M. W., Aisen, P. S., Shaw, L. M., Vemuri, P., Wiste, H. J., Weigand, S. D., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70291-0 · Cited by 4,396
Clinical and biomarker changes in dominantly inherited Alzheimer's disease
Bateman, R. J., Xiong, C., Benzinger, T. L. S., Fagan, A. M., Goate, A., Fox, N. C., Marcus, D. S., Cairns, N. J., Xie, X., Blazey, T. M., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1202753 · Cited by 3,814
Self-citationAlbert, M., DeKosky, S. T., Dickson, D. W., Dubois, B., Feldman, H., Fox, N. C., Gamst, A. C., Holtzman, D. M., Jagust, W. J., Petersen, R. C., et al. (2013) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.11.1.96 · Cited by 2,643
Logan, J., Fowler, J. S., Volkow, N. D., Wolf, A. P., Dewey, S. L., Schlyer, D. J., MacGregor, R. R., HITZEMANN, R. J., Bendriem, B., Gatley, S. J., et al. (1990) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1990.127 · Cited by 1,481
Arnold, S. E., Hyman, B. T., Flory, J., Damasio, A. R., & Van Hoesen, G. W. (1991) · Cerebral Cortex · doi:10.1093/cercor/1.1.103 · Cited by 1,380
Functional Assessment Staging (FAST)
Gauthier, S. G. (2001) · CRC Press eBooks · doi:10.3109/9780203213896-33 · Cited by 1,023
Tau positron emission tomographic imaging in aging and early Alzheimer disease
Johnson, K. A., Schultz, A., Betensky, R. A., Becker, J. A., Sepulcre, J., Rentz, D., Mormino, E., Chhatwal, J., Amariglio, R., Papp, K., et al. (2016) · Annals of Neurology · doi:10.1002/ana.24546 · Cited by 986
Self-citationMolecular mechanisms of neurodegeneration in Alzheimer's disease
Crews, L., & Masliah, E. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq160 · Cited by 772
Flagged first, then by citations
Research works printed but not linked: 1
- [17]17. F]T807. J Labelled Comp Radiopharm. 2013;56(14): 736-740.
Cited by
Sorted by citations
Items 101–101 of 101
Detecting the effect of genetic diversity on brain composition in an Alzheimer’s disease mouse model
Gurdon, B., Yates, S. C., Csucs, G., Groeneboom, N. E., Hadad, N., Telpoukhovskaia, M., Ouellette, A., Ouellette, T., O’Connell, K. M. S., Singh, S., et al. (2024) · Communications Biology · doi:10.1038/s42003-024-06242-1 · Cited by 15
Metadata
- Authors
- Quiroz, Y. T., Sperling, R. A., Norton, D. J., Baena, A., Arboleda-Velasquez, J. F., Cosio, D., Schultz, A., Lapoint, M., Guzman-Velez, E., Miller, J. B., Kim, L. A., Chen, K., Tariot, P. N., Lopera, F., Reiman, E. M., & Johnson, K. A.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Universidad de Antioquia (CO)
- Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston
- Massachusetts General Hospital, Harvard Medical School, Boston
- Massachusetts Eye and Ear Infirmary (US)
- Banner Alzheimer’s Institute (US)
- Corresponding author
- Quiroz, Yakeel T.
- ORCID
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2018-05-01
- Volume
- 75
- Issue
- 5
- Pages
- 548
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC5885174
- OpenAlex
- W2793496929
- Cited by
- 186
- References
- 38
- Citations by year
- 2026: 7 · 2025: 17 · 2024: 18 · 2023: 20 · 2022: 19 · 2021: 30 · 2020: 34 · 2019: 29 · 2018: 12
- FWCI
- 20.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repository University of Antioquia (University of Antioquia) (publishedVersion, cc-by-nc-nd)
- Repositorio Digital - Academia Colombiana de Ciencias Exactas, Fisicas y Naturales (submittedVersion, other-oa)
- Funders
- National Institutes of Health (DP5OD019833)
- National Institute on Aging (K24AG035007, R01AG055444, R01AG046396, R01AG027435, P30AG019610, P50AG005134, P01AG036694, P30AG062421)
- 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
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- autosomal dominant Alzheimer's disease, PSEN1 E280A mutation, presenilin 1, amyloid accumulation, tau accumulation, Pittsburgh compound B PET, flortaucipir PET, preclinical Alzheimer's disease, young adults, medial temporal lobe, neocortex, mild cognitive impairment
- MeSH terms
- Mental Status and Dementia Tests, Adult, Age Factors, Alzheimer Disease, Amyloid, Aniline Compounds, Brain, Carbolines, Cognition Disorders, Colombia, Cross-Sectional Studies, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Mutation, Neuropsychological Tests, Thiazoles, tau Proteins, Positron-Emission Tomography, Presenilin-1
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 2026-10-01, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-01 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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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