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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Claims the paper makes
40 Own result · 26 Not checked yet · 9 Own method · 9 Own interpretation · 4 No basis given
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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 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
plaincorrelationaln = 24- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- 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
“The subgroup of unimpaired carriers also had elevated mean FTP SUVRs in medial temporal regions”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Regional 18F FTP Binding in PSEN1 Mutation Carriers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“In our sample, elevated levels of PiB uptake began around age 30 years.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > 18F FTP and PiB Binding in Relation to Each Other
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“Mutation carriers with MCI had the highest PiB DVR values (mean [SD], 1.53 [0.06]; 95% CI, -0.57 to -0.44)”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Carbon 11-Labeled PiB DVR in PSEN1 Mutation Carriers
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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 higher 18F FTP SUVR binding in the hippocampus (r = 0.70; P = .01)”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Associations Among PET Measures, Age, and Cognitive Measures
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“entorhinal cortex (r = 0.81; P = 02)”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Associations Among PET Measures, Age, and Cognitive Measures
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“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)”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Abstract
plaincorrelationaln = 24 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“Compared with noncarriers, the group of PSEN1 mutation carriers had elevated 18F FTP SUVRs in the entorhinal cortex (mean [SD] SUVR, 1.29 [0.33] vs 1.01 [0.05]; mean difference, -0.28; 95% CI, -0.43 to -0.04; P = .01)”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Regional 18F FTP Binding in PSEN1 Mutation Carriers
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“and inferior temporal (r = 0.74; P = .007)regions”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Associations Among PET Measures, Age, and Cognitive Measures
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“but they differed significantly from noncarriers only in parahippocampal gyrus (mean [SD] SUVR, 1.18 [0.21] vs 1.03 [0.05]; mean difference, -0.15; 95% CI, -0.21 to 0.00; P = .03).”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Regional 18F FTP Binding in PSEN1 Mutation Carriers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“7 of 9 carriers older than 30 years reached the threshold for amyloidosis (distribution volume ratio level > 1.2).”
- Also stated in: § Carbon 11-Labeled PiB DVR in PSEN1 Mutation Carriers · plain
“Seven of 9 mutation carriers 30 years and older reached the threshold for amyloid positivity.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Abstract
plainn = 9- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
- Also stated in: § Carbon 11-Labeled PiB DVR in PSEN1 Mutation Carriers · plain
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
“Elevated levels of tau were not observed in mutation carriers younger than 38 years.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > 18F FTP and PiB Binding in Relation to Each Other
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“At this stage, tracer retention was only observed in the entorhinal cortex”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > 18F FTP and PiB Binding in Relation to Each Other
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“β-Amyloid uptake levels were diffusely elevated in unimpaired carriers approximately 15 years prior to expected onset of mild cognitive impairment.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
- Rests on an assumption: Cross-sectional differences by age reflect the temporal sequence of tau and amyloid accumulation.
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 with increasing age of the carrier, higher tau levels were also observed in the inferior temporal and lateral temporal lobe.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > 18F FTP and PiB Binding in Relation to Each Other
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“and parahippocampal gyrus (mean [SD] SUVR, 1.25 [0.23] vs 1.03 [0.05]; mean difference, -0.22; 95% CI, -0.34 to -0.05; P = .004)”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Regional 18F FTP Binding in PSEN1 Mutation Carriers
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“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.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Abstract
plaincorrelationaln = 9- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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.
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 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)”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Abstract
plaincorrelationaln = 24 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“parahippocampal gyrus (r = 0.74; P = .006)”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Associations Among PET Measures, Age, and Cognitive Measures
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“Greater PiB binding was only associated with CERAD Word List Delayed Recall (r = -0.70;P = .01).”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Associations Among PET Measures, Age, and Cognitive Measures
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“Substantial tau deposition in the neocortex was only observed in 1 unimpaired carrier and in those with mild cognitive impairment.”
- Also stated in: § 18F FTP and PiB Binding in Relation to Each Other · plain
“Flortaucipir F 18 binding in the neocortex was observed in 1 cognitively unimpaired carrier aged 38 years and in all cognitively impaired individuals.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Abstract
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Also stated in: § 18F FTP and PiB Binding in Relation to Each Other · plain
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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“No such relationships were significant in noncarriers.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Associations Among PET Measures, Age, and Cognitive Measures
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“This includes preferential PiB binding in the posterior cingulate, precuneus, parietotemporal, frontal, and basal ganglia regions.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Carbon 11-Labeled PiB DVR in PSEN1 Mutation Carriers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“Greater inferior temporal tau was also related to worse performance on the CERAD Word List Immediate Learning (r = -0.74;P = .006).”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Associations Among PET Measures, Age, and Cognitive Measures
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“In patients with MCI, FTP binding was elevated in widespread neocortical regions, most prominently in inferior and lateral temporo-parietal, parieto-occipital, and posterior cingulate/ precuneus regions (Figure 1).”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Regional 18F FTP Binding in PSEN1 Mutation Carriers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
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
“In addition, this study confirms that clinical symptoms have a greater association with tau pathology than with amyloid pathology.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Conclusions
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Substantial FTP binding in the neocortex is evident in mutation carriers with the highest levels of Aβ.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Conclusions
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Elevated levels of FTP binding are evident within medial temporal lobe regions in amyloid-positive mutation carriers within 10 years of estimated years to symptom onset.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Conclusions
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“With respect to tau, elevated levels of FTP binding in medial temporal lobe regions were only observed in individuals who already showed substantial Aβ deposition in cortical regions.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Downloaded From: https://jamanetwork.com/ on 07/13/2023
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“With respect to amyloid, the present findings confirm that Aβ burden in the preclinical stages of ADAD has a similar spatial distribution as in LOAD and begins more than a decade before the onset of clinical symptoms.29,30”
§ 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 [30] 30. Fleisher AS, Chen K, Quiroz YT, et al. Florbetapir PET analysis of amyloid-β deposition in the presenilin 1 E280A autosomal dominant Alzheimer's disease kindred: a cross-sectional study. Lancet Neurol. 2012;11(12):1057-1065.
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Tau aggregation in the neocortex was observed in individuals with early MCI, consistent with the hypothesis that tau's spread beyond the medial temporal lobe is temporally coupled with cognitive impairment.13”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Downloaded From: https://jamanetwork.com/ on 07/13/2023
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Previously, we showed that unimpaired mutation carriers from this kindred had significantly lower cerebral metabolic rates for glucose, smaller hippocampal volumes, lower cerebrospinal fluid Aβ1-42 measurements, higher cerebrospinal fluid total tau and tau phosphorylated at threonine 181 levels, and higher plasma Aβ1-42 measurements.6”
§ 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 [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.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Previously, we showed that unimpaired mutation carriers from this kindred had significantly lower cerebral metabolic rates for glucose, smaller hippocampal volumes, lower cerebrospinal fluid Aβ1-42 measurements, higher cerebrospinal fluid total tau and tau phosphorylated at threonine 181 levels, and higher plasma Aβ1-42 measurements.6”
§ 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 [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.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In fact, even children and young adults with PSEN1 E280A mutations have alterations in magnetic resonance imaging measurements of brain structure 7,10 and function (eg, hippocampal hyperactivation and less precuneus deactivation) more than 2 decades prior to the kindred's median age of MCI onset.7,10”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Abstract
What the sources say
- Not checked yetcites [7] 7. Reiman EM, Quiroz YT, Fleisher AS, et al. Brain imaging and fluid biomarker analysis in young adults at genetic risk for autosomal dominant Alzheimer's disease in the presenilin 1 E280A kindred: a case-control study. Lancet Neurol. 2012;11 (12):1048-1056.
- Not checked yetcites [10] 10. Quiroz YT, Schultz AP, Chen K, et al. Brain imaging and blood biomarker abnormalities in children with autosomal dominant Alzheimer disease: a cross-sectional study. JAMA Neurol. 2015; 72(8):912-919.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Previously, we showed that unimpaired mutation carriers from this kindred had significantly lower cerebral metabolic rates for glucose, smaller hippocampal volumes, lower cerebrospinal fluid Aβ1-42 measurements, higher cerebrospinal fluid total tau and tau phosphorylated at threonine 181 levels, and higher plasma Aβ1-42 measurements.6”
§ 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 [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.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“With respect to amyloid, the present findings confirm that Aβ burden in the preclinical stages of ADAD has a similar spatial distribution as in LOAD and begins more than a decade before the onset of clinical symptoms.29,30”
§ 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 [30] 30. Fleisher AS, Chen K, Quiroz YT, et al. Florbetapir PET analysis of amyloid-β deposition in the presenilin 1 E280A autosomal dominant Alzheimer's disease kindred: a cross-sectional study. Lancet Neurol. 2012;11(12):1057-1065.
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Previously, we showed that unimpaired mutation carriers from this kindred had significantly lower cerebral metabolic rates for glucose, smaller hippocampal volumes, lower cerebrospinal fluid Aβ1-42 measurements, higher cerebrospinal fluid total tau and tau phosphorylated at threonine 181 levels, and higher plasma Aβ1-42 measurements.6”
§ 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 [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.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 present findings add to the growing evidence that molecular markers can characterize biological changes associated with AD in individuals who are still cognitively unimpaired.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
- Rests on an assumption: Cross-sectional differences by age reflect the temporal sequence of tau and amyloid accumulation.
In the paper
“Previously, we showed that unimpaired mutation carriers from this kindred had significantly lower cerebral metabolic rates for glucose, smaller hippocampal volumes, lower cerebrospinal fluid Aβ1-42 measurements, higher cerebrospinal fluid total tau and tau phosphorylated at threonine 181 levels, and higher plasma Aβ1-42 measurements.6”
§ 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 [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.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 homogeneity of disease course in these mutation carriers allowed us to observe tau and Aβ deposition as a function of individuals' proximity to the expected onset of MCI and dementia.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Downloaded From: https://jamanetwork.com/ on 07/13/2023
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Examination of tau PET in ADAD is particularly relevant to understanding the aggregation and spreading of tau in AD without the major confounders of aging and comorbidities that often exist in sporadic AD.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Previously, we showed that unimpaired mutation carriers from this kindred had significantly lower cerebral metabolic rates for glucose, smaller hippocampal volumes, lower cerebrospinal fluid Aβ1-42 measurements, higher cerebrospinal fluid total tau and tau phosphorylated at threonine 181 levels, and higher plasma Aβ1-42 measurements.6”
§ 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 [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.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The cerebral pattern of Aβ deposition resembled that found in clinically affected individuals who are at risk for LOAD.26”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Carbon 11-Labeled PiB DVR in PSEN1 Mutation Carriers
What the sources say
- Not checked yetcites [26] 26. Mormino EC, Betensky RA, Hedden T, et al. Synergistic effect of β-amyloid and neurodegeneration on cognitive decline in clinically normal individuals. JAMA Neurol. 2014;71(11): 1379-1385.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
In the paper
“Biomarker investigations of families with ADAD have already shed light on the trajectory of ADrelated brain changes, especially prior to the onset of clinical symptoms.[6][7][8]”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Abstract
What the sources say
- Not checked yetcites [6][7][8]
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“This study as well as the present study found that tau deposition in ADAD had a similar spatial pro-file compared with LOAD.”
§ 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 [34] 34. Benzinger TLS, Gordon BA, Friedrichsen KA, et al; Dominantly Inherited Alzheimer Network (DIAN) Study Group. Tau PET imaging with AV-1451 in autosomal dominant Alzheimer's disease: update from the Dominantly Inherited Alzheimer Network (DIAN). Alzheimers Dement. 2016;12(7, suppl):378. doi:10.1016/j.jalz.2016.06.709
plainn = 63- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 present findings add to the growing evidence that molecular markers can characterize biological changes associated with AD in individuals who are still cognitively unimpaired.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Conclusions
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“This was especially the case when examining the subsamples of unimpaired and impaired individuals within the mutation carrier group.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Limitations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“With respect to Aβ, DIAN showed that, averaging across mutations, individuals with preclinical ADAD showed diffuse cortical PiB elevation years before the estimated age of onset for each individual's family.31,32”
§ 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 [31] 31. Fleisher AS, Chen K, Liu X, et al. Using positron emission tomography and florbetapir F18 to image cortical amyloid in patients with mild cognitive impairment or dementia due to Alzheimer disease. Arch Neurol. 2011;68(11):1404-1411.
- Not checked yetcites [32] 32. Benzinger TL, Blazey T, Jack CR Jr, et al. Regional variability of imaging biomarkers in autosomal dominant Alzheimer's disease. Proc Natl Acad Sci U S A. 2013;110(47):E4502-E4509.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Further, in LOAD, there was notable interindividual variability in tau extension at that CDR. 13”
§ 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 [13] 13. Aguirre-Acevedo DC, Gómez RD, Moreno S, et al. Validity and reliability of the CERAD-Col neuropsychological battery [in Spanish]. Rev Neurol. 2007;45(11):655-660.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 lack of apparent tau deposition in the neocortex until roughly 6 years prior to MCI combined with the diffuse spatial profile of tau deposition in patients with MCI suggests that tau spreads rapidly once it begins to aggregate in the cortex.”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Downloaded From: https://jamanetwork.com/ on 07/13/2023
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Tau aggregation in the neocortex was observed in individuals with early MCI, consistent with the hypothesis that tau's spread beyond the medial temporal lobe is temporally coupled with cognitive impairment.13”
§ 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 [13] 13. Aguirre-Acevedo DC, Gómez RD, Moreno S, et al. Validity and reliability of the CERAD-Col neuropsychological battery [in Spanish]. Rev Neurol. 2007;45(11):655-660.
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plainn = 9- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plainn = 9- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.”
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?
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.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Abstract
“inferior temporal lobe: r = -0.54;P = .06”
§ Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease > Discussion
“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
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
The Amyloid-β Pathway in Alzheimer’s Disease
Hampel, H., Hardy, J., Blennow, K., Chen, C., Perry, G., Kim, S. H., Villemagne, V. L., Aisen, P., Vendruscolo, M., Iwatsubo, T., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01249-0 · Cited by 1,952
Palmqvist, S., Janelidze, S., Quiroz, Y. T., Zetterberg, H., Lopera, F., Stomrud, E., Su, Y., Chen, Y., Serrano, G. E., Leuzy, A., et al. (2020) · JAMA · doi:10.1001/jama.2020.12134 · Cited by 1,603
Self-citationthe Dominantly Inherited Alzheimer Network, Barthélemy, N. R., Li, Y., Joseph-Mathurin, N., Gordon, B. A., Hassenstab, J., Benzinger, T. L. S., Buckles, V., Fagan, A. M., Perrin, R. J., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0781-z · Cited by 651
Imaging the evolution and pathophysiology of Alzheimer disease
Jagust, W. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0067-3 · Cited by 604
Arboleda-Velasquez, J. F., Lopera, F., O’Hare, M., Delgado-Tirado, S., Marino, C., Chmielewska, N., Saez-Torres, K. L., Amarnani, D., Schultz, A. P., Sperling, R. A., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0611-3 · Cited by 598
Self-citation
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).
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