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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- Findingown data
Unimpaired mutation carriers had a mean PiB distribution volume ratio of 1.21 (SD 0.14; 95% CI -0.24 to -0.08).
“followed by unimpaired mutation carriers (mean [SD], 1.21 [0.14]; 95% CI, -0.24 to -0.08)”
Quote in the paperNot a substantial claim- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
- Findingown data
In unimpaired mutation carriers, β-amyloid uptake was diffusely increased about 15 years before the expected onset of mild cognitive impairment.
“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.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [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 in the free run.
- cites [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.
Not checked in the free run.
- Also stated in: § Downloaded From: https://jamanetwork.com/ on 07/13/2023 · hedged
- Findingown data
Unimpaired mutation carriers had higher PiB distribution volume ratio than noncarriers, whose mean was 1.04 (SD 0.02; P < .001).
“who in turn showed higher carbon 11-labeled PiB DVR than noncarriers (mean [SD], 1.04 [0.02]; P < .001).”
Quote in the paperSubstantial claim- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
- Findingown data
In PSEN1 E280A carriers, higher entorhinal tau deposition was associated with worse CERAD Word List Delayed Recall performance (r = -0.86, P < .001).
“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).”
Quote in the paperSubstantial claim- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Findingown data
Compared with noncarriers, PSEN1 mutation carriers had elevated 18F FTP SUVR in hippocampus (mean 1.37 vs 1.12; mean difference -0.25; 95% CI -0.49 to -0.03; P = .03).
“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)”
Quote in the paperSubstantial claim- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Findingown data
In mutation carriers, inferior temporal lobe 18F FTP binding was associated with higher mean cortical PiB retention (r = 0.67, P = .02).
“Inferior temporal lobe 18F FTP binding was associated with higher mean cortical PiB retention in mutation carriers (r = 0.67; P = .02).”
Quote in the paperSubstantial claim- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
- Findingnone given
18F FTP SUVR levels were correlated with clinical measures.
“Furthermore, 18F FTP SUVR levels were correlated with clinical measures.”
Quote in the paperNot a substantial claim - Findingown data
In cognitively unimpaired PSEN1 E280A mutation carriers, mean cortical PiB distribution volume ratio was higher than in noncarriers by the late 20s.
“Compared with noncarriers, cognitively unimpaired mutation carriers had elevated mean cortical Pittsburgh Compound B distribution volume ratio levels in their late 20s”
Quote in the paperSubstantial claim- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
- Findingown data
In mutation carriers, greater age was associated with higher cortical PiB distribution volume ratio (r = 0.88, P < .001).
“In mutation carriers, greater age was associated with both higher cortical PiB DVR (r = 0.88; P < .001)”
Quote in the paperSubstantial claim- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
- Findingown data
Among unimpaired carriers, those with the highest PiB distribution volume ratio values also had the highest FTP binding in medial temporal lobe and inferior temporal regions.
“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.”
Quote in the paperSubstantial claim- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
- Findingown data
In cognitively unimpaired PSEN1 mutation carriers, mean FTP SUVRs were elevated in medial temporal regions.
“The subgroup of unimpaired carriers also had elevated mean FTP SUVRs in medial temporal regions”
Quote in the paperSubstantial claim- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Findingown data
In this sample, elevated PiB uptake began around age 30 years.
“In our sample, elevated levels of PiB uptake began around age 30 years.”
Quote in the paperNot a substantial claim- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
- Findingown data
Mutation carriers with mild cognitive impairment had the highest PiB distribution volume ratio values (mean 1.53, SD 0.06; 95% CI -0.57 to -0.44).
“Mutation carriers with MCI had the highest PiB DVR values (mean [SD], 1.53 [0.06]; 95% CI, -0.57 to -0.44)”
Quote in the paperNot a substantial claim- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
- Findingown data
In mutation carriers, greater age was associated with higher 18F FTP SUVR in hippocampus (r = 0.70, P = .01).
“and higher 18F FTP SUVR binding in the hippocampus (r = 0.70; P = .01)”
Quote in the paperSubstantial claim- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Findingown data
In mutation carriers, greater age was associated with higher 18F FTP SUVR in entorhinal cortex (r = 0.81, P = .02).
“entorhinal cortex (r = 0.81; P = 02)”
Quote in the paperSubstantial claim- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Findingown data
In PSEN1 E280A carriers, higher inferior temporal tau deposition was associated with worse Mini-Mental State Examination performance (r = -0.54, P = .06).
“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)”
Quote in the paperSubstantial claim- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Findingown data
Compared with noncarriers, PSEN1 mutation carriers had elevated 18F FTP SUVR in entorhinal cortex (mean 1.29 vs 1.01; mean difference -0.28; 95% CI -0.43 to -0.04; P = .01).
“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)”
Quote in the paperSubstantial claim- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Findingown data
In mutation carriers, greater age was associated with higher 18F FTP SUVR in inferior temporal region (r = 0.74, P = .007).
“and inferior temporal (r = 0.74; P = .007)regions”
Quote in the paperSubstantial claim- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Findingown data
In cognitively unimpaired PSEN1 mutation carriers, the only medial temporal region with significantly higher FTP SUVR than noncarriers was parahippocampal gyrus (mean 1.18 vs 1.03; mean difference -0.15; 95% CI -0.21 to 0.00; P = .03).
“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).”
Quote in the paperSubstantial claim- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Findingown data
Seven of nine PSEN1 E280A carriers aged 30 years or older reached the threshold for amyloid positivity, defined as PiB distribution volume ratio above 1.2.
“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.”
Quote in the paperSubstantial claim- 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
- Findingown data
Elevated tau was not observed in mutation carriers younger than 38 years.
“Elevated levels of tau were not observed in mutation carriers younger than 38 years.”
Quote in the paperSubstantial claim- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Findingown data
At the stage when tau tracer retention was first observed, it was only in the entorhinal cortex.
“At this stage, tracer retention was only observed in the entorhinal cortex”
Quote in the paperNot a substantial claim- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Findingown data
In unimpaired PSEN1 E280A carriers, β-amyloid uptake was diffusely elevated approximately 15 years before the expected onset of mild cognitive impairment.
“β-Amyloid uptake levels were diffusely elevated in unimpaired carriers approximately 15 years prior to expected onset of mild cognitive impairment.”
Quote in the paperSubstantial claim- 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.
- Findingown data
With increasing age of the carrier, higher tau levels were also observed in inferior temporal and lateral temporal lobe.
“and with increasing age of the carrier, higher tau levels were also observed in the inferior temporal and lateral temporal lobe.”
Quote in the paperSubstantial claim- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Findingown data
Compared with noncarriers, PSEN1 mutation carriers had elevated 18F FTP SUVR in parahippocampal gyrus (mean 1.25 vs 1.03; mean difference -0.22; 95% CI -0.34 to -0.05; P = .004).
“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)”
Quote in the paperSubstantial claim- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Findingown data
In amyloid-positive PSEN1 E280A carriers, elevated tau deposition was present in medial temporal lobe regions about six years before the expected clinical onset of Alzheimer disease.
“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.”
Quote in the paperSubstantial claim- 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.
- Findingown data
In PSEN1 E280A carriers, higher entorhinal tau deposition was associated with worse Mini-Mental State Examination performance (r = -0.60, P = .04).
“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)”
Quote in the paperSubstantial claim- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Findingown data
In mutation carriers, greater age was associated with higher 18F FTP SUVR in parahippocampal gyrus (r = 0.74, P = .006).
“parahippocampal gyrus (r = 0.74; P = .006)”
Quote in the paperSubstantial claim- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Findingown data
In mutation carriers, greater PiB binding was associated only with CERAD Word List Delayed Recall performance (r = -0.70, P = .01).
“Greater PiB binding was only associated with CERAD Word List Delayed Recall (r = -0.70;P = .01).”
Quote in the paperNot a substantial claim- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
- Findingown data
Substantial tau deposition in the neocortex occurred only in one cognitively unimpaired carrier and in carriers with mild cognitive impairment.
“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.”
Quote in the paperSubstantial claim- 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
- Findingown data
In PSEN1 E280A carriers, higher inferior temporal tau deposition was associated with worse CERAD Word List Delayed Recall performance (r = -0.70, P = .01).
“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).”
Quote in the paperSubstantial claim- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Findingown data
In noncarriers, no significant relationships were found between age and the PET measures.
“No such relationships were significant in noncarriers.”
Quote in the paperNot a substantial claim - Findingown data
Aβ deposition included preferential PiB binding in posterior cingulate, precuneus, parietotemporal, frontal, and basal ganglia regions.
“This includes preferential PiB binding in the posterior cingulate, precuneus, parietotemporal, frontal, and basal ganglia regions.”
Quote in the paperNot a substantial claim- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
- Findingown data
In mutation carriers, greater inferior temporal tau was associated with worse CERAD Word List Immediate Learning performance (r = -0.74, P = .006).
“Greater inferior temporal tau was also related to worse performance on the CERAD Word List Immediate Learning (r = -0.74;P = .006).”
Quote in the paperSubstantial claim- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Findingown data
In patients with mild cognitive impairment, FTP binding was elevated in widespread neocortical regions, most prominently inferior and lateral temporo-parietal, parieto-occipital, and posterior cingulate/precuneus regions.
“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).”
Quote in the paperSubstantial claim- Rests on an assumption: Flortaucipir F 18 selectively binds tau aggregates.
- Findingnone given
Clinical symptoms have a greater association with tau pathology than with amyloid pathology.
“In addition, this study confirms that clinical symptoms have a greater association with tau pathology than with amyloid pathology.”
Quote in the paperSubstantial claim - Findingown data
Substantial FTP binding in the neocortex is evident in mutation carriers with the highest levels of Aβ.
“Substantial FTP binding in the neocortex is evident in mutation carriers with the highest levels of Aβ.”
Quote in the paperSubstantial claim - Findingown data
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.
“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.”
Quote in the paperSubstantial claim - Findingown data
Elevated levels of FTP binding in medial temporal lobe regions were only observed in individuals who already showed substantial Aβ deposition in cortical regions.
“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.”
Quote in the paperSubstantial claim - Findingcitation
Aβ burden in preclinical ADAD begins more than a decade before the onset of clinical symptoms.
“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”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [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 in the free run.
- cites [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.
Not checked in the free run.
- Findingcitation
Tau aggregation in the neocortex was observed in individuals with early MCI.
“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”
Quote in the paperSubstantial claim - Premisecitation
Unimpaired mutation carriers from this kindred had significantly lower cerebral metabolic rates for glucose.
“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”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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.
Not checked in the free run.
- Premisecitation
Unimpaired mutation carriers from this kindred had smaller hippocampal volumes.
“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”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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.
Not checked in the free run.
- Premisecitation
Children and young adults with PSEN1 E280A mutations have alterations in MRI measures of brain structure and function more than two decades before the kindred's median age of mild cognitive impairment onset.
“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”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [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 in the free run.
- cites [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.
Not checked in the free run.
- Premisecitation
Unimpaired mutation carriers from this kindred had higher cerebrospinal fluid total tau levels.
“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”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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.
Not checked in the free run.
- Interpretationcitation
Aβ burden in preclinical ADAD has a similar spatial distribution as in LOAD.
“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”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [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 in the free run.
- cites [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.
Not checked in the free run.
- Premisecitation
Unimpaired mutation carriers from this kindred had lower cerebrospinal fluid Aβ1-42 measurements.
“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”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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.
Not checked in the free run.
- Interpretationown data
The study findings add to evidence that molecular markers can characterize Alzheimer disease-related biological changes in people who remain cognitively unimpaired.
“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.”
Quote in the paperSubstantial claim- 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.
- Premisecitation
Unimpaired mutation carriers from this kindred had higher cerebrospinal fluid tau phosphorylated at threonine 181 levels.
“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”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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.
Not checked in the free run.
- Study design and conductreasoning
The homogeneity of disease course in these mutation carriers allowed observation of tau and Aβ deposition as a function of proximity to expected onset of MCI and dementia.
“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.”
Quote in the paperSubstantial claim - Premisenone given
Studying tau PET in autosomal dominant Alzheimer disease is particularly relevant for understanding tau aggregation and spread in Alzheimer disease without the major aging and comorbidity confounders common in sporadic Alzheimer disease.
“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.”
Quote in the paperSubstantial claim - Premisecitation
Unimpaired mutation carriers from this kindred had higher plasma Aβ1-42 measurements.
“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”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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.
Not checked in the free run.
- Interpretationcitation
The cerebral pattern of Aβ deposition in carriers resembled that in clinically affected individuals at risk for late-onset Alzheimer disease.
“The cerebral pattern of Aβ deposition resembled that found in clinically affected individuals who are at risk for LOAD.26”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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.
Not checked in the free run.
- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
- Premisecitation
Biomarker studies of autosomal dominant Alzheimer disease families have already clarified the trajectory of Alzheimer disease-related brain changes, especially before clinical symptoms appear.
“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]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6][7][8]
Not checked in the free run.
- Interpretationcitation
Tau deposition in ADAD has a similar spatial profile compared with LOAD.
“This study as well as the present study found that tau deposition in ADAD had a similar spatial pro-file compared with LOAD.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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
Not checked in the free run.
- Interpretationnone given
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 present findings add to the growing evidence that molecular markers can characterize biological changes associated with AD in individuals who are still cognitively unimpaired.”
Quote in the paperSubstantial claim - Study design and conductreasoning
The subsamples of unimpaired and impaired individuals within the mutation carrier group were especially small.
“This was especially the case when examining the subsamples of unimpaired and impaired individuals within the mutation carrier group.”
Quote in the paperNot a substantial claim - Premisecitation
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.
“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”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [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 in the free run.
- cites [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.
Not checked in the free run.
- Premisecitation
In LOAD, there was notable interindividual variability in tau extension at CDR 0.5.
“Further, in LOAD, there was notable interindividual variability in tau extension at that CDR. 13”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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.
Not checked in the free run.
- Interpretationreasoning
Tau spreads rapidly once it begins to aggregate in the cortex.
“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.”
Quote in the paperSubstantial claim - Interpretationcitation
Tau's spread beyond the medial temporal lobe is temporally coupled with cognitive impairment.
“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”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [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.
Not checked in the free run.
- May combine two claims. 14
- Classified as probably not a substantial claim. 16
May combine two claims.
Findingown dataThe youngest mutation carrier, aged 28 years, had no PiB elevation, with a PiB value of 1.02.
“The youngest mutation carrier, aged 28 years, showed no PIB elevation (PiB = 1.02)”
Quote in the paperNot a substantial claim- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
May combine two claims.
Findingown dataNo noncarriers showed elevated amyloid accumulation; all had PiB distribution volume ratio below 1.1.
“No elevated amyloid accumulation was seen in any noncarriers, as expected (PiB DVR < 1.1 in all individuals).”
Quote in the paperNot a substantial claim- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
May combine two claims.
Findingown dataCompared with unimpaired mutation carriers, cognitively impaired mutation carriers were older and had significantly lower neuropsychological test scores.
“Compared with unimpaired mutation carriers, cognitively impaired mutation carriers were older and had significantly lower neuropsychological test scores.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataStarting at age 29 years, mutation carriers showed elevated PiB uptake, with PiB distribution volume ratio above 1.1 in all but one individual.
“but beginning at age 29 years, mutation carriers showed elevated PiB uptake (PiB DVR > 1.1 in all but 1 individual).”
Quote in the paperSubstantial claim- Rests on an assumption: Carbon 11-labeled PiB selectively binds amyloid deposits.
Classified as probably not a substantial claim.
PremisereasoningCombining tau PET with PiB PET can show the extent to which amyloid-tau relationships in autosomal dominant Alzheimer disease differ from those in sporadic Alzheimer disease.
“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.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAll data were acquired by investigators who were masked to participants' genetic status.
“All data were acquired by investigators who were masked to the participants' genetic status.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationPSEN1 mutations predispose people to autosomal dominant Alzheimer disease, usually in relatively early adulthood.
“Presenilin 1 (PSEN1; OMIM, 104311) mutations predispose individuals to develop autosomal dominant Alzheimer disease (ADAD), usually relatively early in adulthood.5”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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.
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenPET data were not partial volume corrected.
“Positron emission tomography data were not partial volume corrected.”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductown dataThe cognitively unimpaired mutation carrier and noncarrier groups did not differ significantly in age, sex, education, or neuropsychological test scores.
“The cognitively unimpaired mutation carrier and noncarrier groups did not differ significantly in their age, sex, education, or neuropsycho-logical test scores.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).
PremisecitationAlzheimer disease is defined at the neuropathological molecular level by amyloid plaques and neurofibrillary tangles.
“A lzheimer disease (AD) is defined at the neuropathological molecular level by amyloid plaques and neurofibrillary tangles.1,2”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [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 in the free run.
- cites [2] 2. Crews L, Masliah E. Molecular mechanisms of neurodegeneration in Alzheimer's disease. Hum Mol Genet. 2010;19(R1):R12-R20.
Not checked in the free run.
May combine two claims.
PremisecitationAbout 30% of living mutation carriers in this kindred currently have Alzheimer disease symptoms, with median ages of 44 years at mild cognitive impairment onset and 49 years at dementia onset.
“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”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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.
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationAlzheimer disease neuropathology has a characteristic spatial distribution: amyloid plaques start in neocortical association areas, while tangles start in the medial temporal lobe and later spread into adjacent association cortices and then across the cortex.
“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”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [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 in the free run.
- cites [4] 4. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991; 82(4):239-259.
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThe PSEN1 E280A kindred in Antioquia, Colombia is estimated to include about 5000 living members, of whom about 1800 carry the mutation.
“Residing in Antioquia, Colombia, this kindred is estimated to have approximately 5000 living members, including approximately 1800 mutation carriers.9”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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.
Not checked in the free run.
May combine two claims.
Interpretationown dataTau PET imaging may be useful as a biomarker for identifying individuals at high risk of developing clinical Alzheimer disease symptoms and for tracking disease progression.
“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.”
Quote in the paperSubstantial claim- 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.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductcitationFlortaucipir F 18 was validated for human use.
“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”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [16] 16. Shoup TM, Yokell DL, Rice PA, et al. A concise radiosynthesis of the tau radiopharmaceutical, [(18)
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenEach PET frame was checked for adequate count statistics and absence of head motion.
“Positron emission tomography images were reconstructed and attenuation-corrected, and each frame was evaluated to verify adequate count statistics and absence of head motion.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductnone givenCognitively unimpaired mutation carriers and noncarriers were matched for sex, age, and education.
“Cognitively unimpaired mutation carriers and noncarriers were matched for sex, age, and education.”
Quote in the paperSubstantial claimMay combine two claims.
Study design and conductown dataPiB and FTP analyses using white matter as the reference gave results very similar to those using cerebellum; statistical differences seen with cerebellum were also seen with white matter.
“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).”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductcitationA linear regression was used to regress choroid plexus signal to account for possible 18F FTP off-target binding that could confound hippocampal signal.
“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”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [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.
Not checked in the free run.
May combine two claims.
PremisecitationAlthough autosomal dominant Alzheimer disease may differ from late-onset Alzheimer disease in pathogenesis and some clinical features, the two conditions are markedly similar in biological profiles, including amyloid biomarkers, brain structure, and brain activity.
“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”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [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.
Not checked in the free run.
May combine two claims.
InterpretationreasoningTau 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.
“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.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
InterpretationreasoningCross-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.
“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.”
Quote in the paperSubstantial claim- Rests on an assumption: Age is predictive of clinical onset in the PSEN1 E280A mutation kindred.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe present results are based on a relatively small sample size compared with studies of LOAD.
“In addition, the present results are based on a relatively small sample size compared with studies of LOAD.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).
InterpretationcitationThese findings will inform ongoing preclinical trials with ADAD, such as the Alzheimer Prevention Initiative treatment trial of an Aβ-modifying agent.
“These findings will inform ongoing preclinical trials with ADAD, such as the Alzheimer Prevention Initiative treatment trial of an Aβ-modifying agent.35”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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.
Not checked in the free run.
May combine two claims.
InterpretationreasoningThe results from the Colombia kindred agree with those from DIAN for both FTP and PiB imaging.
“Overall, the results from the Colombia kindred agree with those from DIAN for both FTP and PiB imaging.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningThe temporal differences observed between amyloid and tau pathology in this study may be explained in part by limited detection of pathology by PET methods.
“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.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Interpretationnone givenThere is uncertainty regarding the extent to which the findings will generalize to LOAD and to other AD-causing mutations.
“Most importantly, there is uncertainty regarding the extent to which the findings will generalize to LOAD and to other AD-causing mutations.”
Quote in the paperNot a substantial claim
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 reported patient was protected from clinical effects of PSEN1-E280A, a highly penetrant EOAD mutation, for 28 years by the homozygous APOE3-R136S mutation.
“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 male case had relatively limited Tau pathology in the entorhinal cortex (SUVR = 1.34) and in other neocortical regions such as PCC (SUVR = 1.51) and precuneus (SUVR = 1.49).
“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]
The Regional 18F FTP Binding section reports group-level SUVRs and describes binding in the posterior cingulate/precuneus, but does not report the stated values for a male case. Searches for the three SUVR values and for a male case found no matching passage in our copy. (LLM, conf=0.73)
Experimental — accuracy not yet measuredLongitudinal measures show that soluble tau phosphorylation occupancy falls while tau rises, at least in DIAD, indicating an inverse correlation.
“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”
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 2,630 · see citing works
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 · see citing works
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 · see citing works
Functional Assessment Staging (FAST)
Gauthier, S. G. (2001) · CRC Press eBooks · doi:10.3109/9780203213896-33 · Cited by 1,023 · see citing works
Tau positron emission tomographic imaging in aging and early <scp>A</scp> lzheimer 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 · see citing works
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 · see citing works
Early Clinical PET Imaging Results with the Novel PHF-Tau Radioligand [F18]-T808
Chien, D. T., Szardenings, A. K., Bahri, S., Walsh, J. C., Mu, F., Xia, C. A., Shankle, W. R., Lerner, A. J., Su, M., Elizarov, A. M., et al. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-130098 · Cited by 676 · see citing works
Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807
Chien, D. T., Bahri, S., Szardenings, A. K., Walsh, J. C., Mu, F., Su, M.-Y., Shankle, W. R., Elizarov, A., & Kolb, H. C. (2013) · Journal of Alzheimer's Disease · doi:10.3233/jad-122059 · Cited by 651 · see citing works
Disruption of Functional Connectivity in Clinically Normal Older Adults Harboring Amyloid Burden
Hedden, T., Van Dijk, K. R. A., Becker, J. A., Mehta, A., Sperling, R. A., Johnson, K. A., & Buckner, R. L. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3189-09.2009 · Cited by 598 · see citing works
Self-citationReiman, E. M., Quiroz, Y. T., Fleisher, A. S., Chen, K., Velez-Pardo, C., Jimenez-Del-Rio, M., Fagan, A. M., Shah, A. R., Alvarez, S., Arbelaez, A., et al. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70228-4 · Cited by 541 · see citing works
Self-citationDiagnostic Criteria for Neuropathologic Assessment of Alzheimer’s Disease
Braak, H., & Braak, E. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00062-6 · Cited by 410 · see citing works
Regional variability of imaging biomarkers in autosomal dominant Alzheimer's disease
Benzinger, T. L. S., Blazey, T., Jack, C. R., Koeppe, R. A., Su, Y., Xiong, C., Raichle, M. E., Snyder, A. Z., Ances, B. M., Bateman, R. J., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1317918110 · Cited by 391 · see citing works
Self-citationFleisher, A. S. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.150 · Cited by 364 · see citing works
Lopera, F. (1997) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1997.03540340027028 · Cited by 351 · see citing works
Self-citationAmyloid‐β associated cortical thinning in clinically normal elderly
Becker, J. A., Hedden, T., Carmasin, J., Maye, J., Rentz, D. M., Putcha, D., Fischl, B., Greve, D. N., Marshall, G. A., Salloway, S., et al. (2011) · Annals of Neurology · doi:10.1002/ana.22333 · Cited by 342 · see citing works
Self-citationAlzheimer's Prevention Initiative: A Plan to Accelerate the Evaluation of Presymptomatic Treatments
Reiman, E. M., Langbaum, J. B. S., Fleisher, A., Caselli, R. J., Chen, K., Ayutyanont, N., Quiroz, Y. T., Kosik, K. S., Lopera, F. J., & Tariot, P. N. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-0059 · Cited by 340 · see citing works
Self-citationMormino, E. C., Betensky, R. A., Hedden, T., Schultz, A. P., Amariglio, R. E., Rentz, D. M., Johnson, K. A., & Sperling, R. A. (2014) · JAMA Neurology · doi:10.1001/jamaneurol.2014.2031 · Cited by 328 · see citing works
Self-citationWang, L. Y., Benzinger, T. L. S., Su, Y., Christensen, J. J., Friedrichsen, K. A., Aldea, P., McConathy, J., Cairns, N. J., Fagan, A. M., Morris, J. C., et al. (2016) · JAMA Neurology · doi:10.1001/jamaneurol.2016.2078 · Cited by 295 · see citing works
Acosta-Baena, N., Sepulveda-Falla, D., Lopera-Gómez, C. M., Jaramillo-Elorza, M. C., Moreno, S., Aguirre-Acevedo, D. C., Saldarriaga, A., & Lopera, F. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70323-9 · Cited by 263 · see citing works
Self-citationLopera, F. J. (1997) · JAMA · doi:10.1001/jama.277.10.793 · Cited by 255 · see citing works
Self-citationFleisher, A., Chen, K., Quiroz, Y. T., Jakimovich, L. J., Gomez, M. G., Langois, C. M., Langbaum, J. B. S., Ayutyanont, N., Roontiva, A., Thiyyagura, P., et al. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70227-2 · Cited by 242 · see citing works
Self-citationDiagnostic criteria for the neuropathologic assessment of Alzheimer's disease.
Powers, J. M. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00070-5 · Cited by 214 · see citing works
Fleisher, A. S., Chen, K., Quiroz, Y. T., Jakimovich, L. J., Gutierrez Gomez, M., Langois, C. M., Langbaum, J. B. S., Roontiva, A., Thiyyagura, P., Lee, W., et al. (2015) · JAMA Neurology · doi:10.1001/jamaneurol.2014.3314 · Cited by 177 · see citing works
Self-citationSubjective cognitive concerns, amyloid-β, and neurodegeneration in clinically normal elderly
Amariglio, R. E., Mormino, E. C., Pietras, A., Marshall, G. A., Vannini, P., Johnson, K. A., Sperling, R. A., & Rentz, D. M. (2015) · Neurology · doi:10.1212/wnl.0000000000001712 · Cited by 166 · see citing works
Self-citationVulnerability of cortical neurons to Alzheimer's and Parkinson's diseases
Braak, H., Rüb, U., Schultz, C., & Tredici, K. D. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-9s305 · Cited by 163 · see citing works
Familial and sporadic Alzheimer's disease
Lippa, C. F., Saunders, A. M., Smith, T. W., Swearer, J. M., Drachman, D. A., Ghetti, B. F., Nee, L., Pulaski-Salo, D., Dickson, D. W., Robitaille, Y., et al. (1996) · Neurology · doi:10.1212/wnl.46.2.406 · Cited by 127 · see citing works
Sperling, R. A., Johnson, K. A., Doraiswamy, P. M., Reiman, E. M., Fleisher, A., Sabbagh, M. N., Sadowsky, C., Carpenter, A. P., Davis, M. D., Lu, M., et al. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.06.014 · Cited by 123 · see citing works
Self-citationQuiroz, Y. T., Schultz, A. P., Chen, K., Protas, H. D., Brickhouse, M. J., Fleisher, A., Langbaum, J. B. S., Thiyyagura, P., Fagan, A. M., Shah, A. R., et al. (2015) · JAMA Neurology · doi:10.1001/jamaneurol.2015.1099 · Cited by 120 · see citing works
Self-citation[Validity and reliability of the CERAD-Col neuropsychological battery].
Aguirre–Acevedo, D. C., Gómez, R. D., Moreno, S., Henao, E., Motta, M., Muñoz, C., Arana, A., Pineda, D. A., & Lopera, F. J. (2007) · PubMed · Cited by 83 · see citing works
Self-citationDeposition of Hyperphosphorylated Tau in Cerebellum of PS1 E280A Alzheimer's Disease
Sepulveda‐Falla, D., Matschke, J., Bernreuther, C., Hagel, C., Puig, B., Villegas, A., Garcia, G., Zea, J., Gomez‐Mancilla, B., Ferrer, I., et al. (2011) · Brain Pathology · doi:10.1111/j.1750-3639.2010.00469.x · Cited by 82 · see citing works
Self-citationA concise radiosynthesis of the tau radiopharmaceutical, [18F]T807
Shoup, T. M., Yokell, D. L., Rice, P. A., Jackson, R. N., Livni, E., Johnson, K. A., Brady, T. J., & Vasdev, N. (2013) · Journal of Labelled Compounds and Radiopharmaceuticals · doi:10.1002/jlcr.3098 · Cited by 80 · see citing works
Self-citationNeurofibrillary pathology leads to synaptic loss and not the other way around in Alzheimer disease
Iqbal, K., & Grundke, I. (2002) · Journal of Alzheimer s Disease · doi:10.3233/jad-2002-4313 · Cited by 56 · see citing works
Benzinger, T. L. S., Gordon, B. A., Friedrichsen, K. A., et al. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.06.709 · Cited by 5 · see citing works
Opportunities for and Obstacles to Treatments for Dementias
Yesavage, J. A. (1983) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1983.tb06290.x · Cited by 5 · see citing works
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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 · see citing works
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 · see citing works
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 · see citing works
Imaging the evolution and pathophysiology of Alzheimer disease
Jagust, W. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0067-3 · Cited by 604 · see citing works
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 · see citing works
Self-citationAmyloid-β-independent regulators of tau pathology in Alzheimer disease
van der Kant, R., Goldstein, L. S. B., & Ossenkoppele, R. (2020) · Nature reviews. Neuroscience · doi:10.1038/s41583-019-0240-3 · Cited by 580 · see citing works
Tau impairs neural circuits, dominating amyloid-β effects, in Alzheimer models in vivo
Busche, M. A., Wegmann, S., Dujardin, S., Commins, C., Schiantarelli, J., Klickstein, N., Kamath, T. V., Carlson, G. A., Nelken, I., & Hyman, B. T. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0289-8 · Cited by 413 · see citing works
Suárez‐Calvet, M., Karikari, T. K., Ashton, N. J., Lantero Rodríguez, J., Milà‐Alomà, M., Gispert, J. D., Salvadó, G., Minguillon, C., Fauria, K., Shekari, M., et al. (2020) · EMBO Molecular Medicine · doi:10.15252/emmm.202012921 · Cited by 401 · see citing works
“…studies on the timing of the biomarker’s changes in sporadic or autosomaldominant AD suggest that CSF p-tau increases earlier in the disease than tau PET (Bateman et al, 2012; Toledo et al, 2013; Johnson et al, 2016; Quiroz et al, 2018; Gordon et al, 2019; Jack et al, 2019; Mattsson et al, 2019).”
BackgroundThe complexity of tau in Alzheimer’s disease
Naseri, N. N., Wang, H., Guo, J. D., Sharma, M., & Luo, W. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.04.022 · Cited by 374 · see citing works
“the neocortex was associated with mild cognitive impairment and worse scores on cognitive tests [287].”
BackgroundAntisense Oligonucleotide Therapies for Neurodegenerative Diseases
Bennett, C. F., Krainer, A. R., & Cleveland, D. W. (2019) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-070918-050501 · Cited by 353 · see citing works
“With newer in vivo imaging techniques and CSF measurements of β-amyloid and tau in a genetically predisposed patient population, the temporal relationship between these two pathologies has become better defined (Fleisher et al. 2015, McDade & Bateman 2018, McDade et al. 2018, Quiroz et al. 2018).”
BackgroundRadiopharmaceuticals for PET and SPECT Imaging: A Literature Review over the Last Decade
Crișan, G., Moldovean-Cioroianu, N. S., Timaru, D.-G., Andrieș, G., Căinap, C., & Chiș, V. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23095023 · Cited by 283 · see citing works
A walk through tau therapeutic strategies
Jadhav, S., Ávila, J., Schöll, M., Kovács, G. G., Kövari, E., Škrabana, R., Evans, L., Kontseková, E., Malawska, B., de Silva, R., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0664-z · Cited by 286 · see citing works
Therriault, J., Vermeiren, M. R., Servaes, S., Tissot, C., Ashton, N. J., Benedet, A. L., Karikari, T. K., Lantero‐Rodriguez, J., Brum, W. S., Lussier, F. Z., et al. (2022) · JAMA Neurology · doi:10.1001/jamaneurol.2022.4485 · Cited by 268 · see citing works
Leuzy, A., Smith, R., Ossenkoppele, R., Santillo, A., Borroni, E., Klein, G., Ohlsson, T., Jögi, J., Palmqvist, S., Mattsson-Carlgren, N., et al. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2020.0989 · Cited by 222 · see citing works
Schöll, M., Maaß, A., Mattsson, N., Ashton, N. J., Blennow, K., Zetterberg, H., & Jagust, W. J. (2018) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2018.12.001 · Cited by 227 · see citing works
“Data from studies in early-onset familial/autosomal-dominant AD are limited, suggesting earliest FTP uptake in the MTL of Aβ-positive presymptomatic mutation carriers but high cortical uptake, spatially comparable to sporadic EOAD cases in later symptomatic stages (Quiroz et al., 2018; Schöll et al., 2017a).”
ResultMorris, G. P., Clark, I. A., & Vissel, B. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1918-8 · Cited by 212 · see citing works
Sanchez, J. S., Becker, J. A., Jacobs, H. I. L., Hanseeuw, B. J., Jiang, S., Schultz, A. P., Properzi, M. J., Katz, S. R., Beiser, A., Satizabal, C. L., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abc0655 · Cited by 200 · see citing works
Self-citationResilience to autosomal dominant Alzheimer’s disease in a Reelin-COLBOS heterozygous man
Lopera, F., Marino, C., Chandrahas, A. S., O’Hare, M., Villalba-Moreno, N. D., Aguillon, D., Baena, A., Sanchez, J. S., Vila-Castelar, C., Ramirez Gomez, L., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02318-3 · Cited by 192 · see citing works
Self-citationGordon, B. A., Blazey, T. M., Christensen, J., Dincer, A., Flores, S., Keefe, S., Chen, C., Su, Y., McDade, E. M., Wang, G., et al. (2019) · Brain · doi:10.1093/brain/awz019 · Cited by 180 · see citing works
“While tau PET has been examined in ADAD (Smith et al., 2016; Quiroz et al., 2018), this work had very small samples of impaired individuals (53), and had limited additional biomarkers.”
BackgroundResultQuiroz, Y. T., Zetterberg, H., Reiman, E. M., Chen, Y., Su, Y., Fox-Fuller, J. T., Garcia, G., Villegas, A., Sepulveda-Falla, D., Villada, M., et al. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30137-x · Cited by 159 · see citing works
Self-citationDissecting the clinical heterogeneity of early-onset Alzheimer’s disease
Sirkis, D. W., Bonham, L. W., Johnson, T. P., La Joie, R., & Yokoyama, J. S. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01531-9 · Cited by 151 · see citing works
Dementia in Latin America: Paving the way toward a regional action plan
Parra, M. A., Báez, S., Sedeño, L., Campo, C. G., Santamaría‐García, H. A., Aprahamian, I., Bertolucci, P. H. F., Bustin, J., Bicalho, M. A. C., Cano, C. A., et al. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12202 · Cited by 148 · see citing works
Self-citationMiao, J., Shi, R., Li, L., Chen, F., Zhou, Y., Tung, Y. C., Hu, W. H., Gong, C., Iqbal, K., & Liu, F. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00034 · Cited by 127 · see citing works
“plaques, correlates with the degree of dementia in AD patients (Tomlinson et al., 1970; Alafuzoff et al., 1987; Arriagada et al., 1992; Quiroz et al., 2018).”
BackgroundUddin, M. S., Kabir, M. T., Rahman, M. S., Behl, T., Jeandet, P., Ashraf, G. M., Najda, A., Bin-Jumah, M. N., El-Seedi, H. R., & Abdel‐Daim, M. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165858 · Cited by 127 · see citing works
“[45] revealed that increased levels of tau were observed in medial temporal lobe areas in carriers of unimpaired PSEN1 E280A mutation in their late 30s, and that noticeable formation of tau tangle in neocortical areas was seen in one cognitively unaffected carrier as well as in individuals with mild cognitive impairme…”
BackgroundMcCluskey, S. P., Plisson, C., Rabiner, E. A., & Howes, O. D. (2019) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-019-04488-0 · Cited by 121 · see citing works
Nelson, M. R., Liu, P., Agrawal, A., Yip, O., Blumenfeld, J., Traglia, M., Kim, M. J., Koutsodendris, N., Rao, A., Grone, B., et al. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01480-8 · Cited by 118 · see citing works
“The reported patient was protected from the clinical effects of PSEN1-E280A, a highly pene-trant mutation causing EOAD dementia 41,42 , for 28 years by the homozygous APOE3-R136S mutation 36 .”
BackgroundSelf-citationMilligan Armstrong, A., Porter, T., Quek, H., White, A., Haynes, J., Jackaman, C., Villemagne, V., Munyard, K., Laws, S. M., Verdile, G., et al. (2021) · Biological Reviews · doi:10.1111/brv.12750 · Cited by 116 · see citing works
Kalaria, R. N., Maestre, G. E., Mahinrad, S., Acosta, D. M., Akinyemi, R., Alladi, S., Allegri, R., Arshad, F., Babalola, D. O., Baiyewu, O., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13836 · Cited by 102 · see citing works
“153 In addition, PSEN1 E280A carriers have low levels of cerebrospinal fluid (CSF) A β 1-42 154 and high levels of plasma tau phosphorylated at threonine 217 (p-tau217) and neurofilament light (NfL) up to 20 years before the first symptoms of MCI.”
Sepulveda-Falla, D., Sanchez, J. S., Almeida, M. C., Boassa, D., Acosta-Uribe, J., Vila-Castelar, C., Ramirez-Gomez, L., Baena, A., Aguillon, D., Villalba-Moreno, N. D., et al. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02467-8 · Cited by 92 · see citing works
“Structural MRI, 11C-Pittsburgh Compound B (PiB) and 18F-Flortaucipir (FTP) PET data were acquired at Massachusetts General Hospital, as previously described [29].”
MethodSelf-citationGuzmán‐Vélez, E., Diez, I. P., Schoemaker, D., Pardilla‐Delgado, E., Vila‐Castelar, C., Fox‐Fuller, J. T., Baena, A. Y., Sperling, R. A., Johnson, K. A., Lopera, F. J., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2113641119 · Cited by 93 · see citing works
“, the preclinical stage)(1, 2) and follows distinct spatio-temporal patterns(3, 4).”
BackgroundSelf-citationLongitudinal tau-PET uptake and atrophy in atypical Alzheimer's disease
Sintini, I., Martin, P. R., Graff‐Radford, J., Senjem, M. L., Schwarz, C. G., Machulda, M. M., Spychalla, A. J., Drubach, D. A., Knopman, D. S., Petersen, R. C., et al. (2019) · NeuroImage Clinical · doi:10.1016/j.nicl.2019.101823 · Cited by 81 · see citing works
“According to the amyloid cascade model, the formation of Aβ plaques triggers the biological events that subsequently cause tauopathy, which is followed by neurodegeneration and, lastly, by the clinical symptoms of dementia (Jack Jr. et al., 2013; Jack et al., 2010; Quiroz et al., 2018).”
BackgroundRelevance of biomarkers across different neurodegenerative diseases
Ehrenberg, A. J., Khatun, A., Coomans, E. M., Betts, M. J., Capraro, F., Thijssen, E. H., Senkevich, K. A., Bharucha, T., Jafarpour, M., Young, P. N. E., et al. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00601-w · Cited by 79 · see citing works
“For example, positron emission tomography (PET) imaging studies of familial AD cases have suggested that brain Aβ deposition begins up to 20 years before clinical symptoms, while cortical tau deposition arises roughly 6 years before onset [39, 40].”
BackgroundCurrent directions in tau research: Highlights from Tau 2020
Sexton, C. E., Snyder, H. M., Beher, D., Boxer, A. L., Brannelly, P., Brion, J., Buée, L., Cacace, A. M., Chételat, G., Citron, M., et al. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12452 · Cited by 78 · see citing works
Self-citationFranzmeier, N., Koutsouleris, N., Benzinger, T. L. S., Goate, A., Karch, C. M. M., Fagan, A. M., McDade, E., Duering, M., Dichgans, M., Levin, J., et al. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12032 · Cited by 73 · see citing works
“43,44 Further, predictive regions included posterior parietal and medial temporal regions for MRI and posterior parietal and lateral frontal regions for FDG-PET, that is, AD-typical predilection sites.”
Sintini, I., Schwarz, C. G., Martin, P. R., Graff‐Radford, J., Machulda, M. M., Senjem, M. L., Reid, R. I., Spychalla, A. J., Drubach, D. A., Lowe, V. J., et al. (2018) · Human Brain Mapping · doi:10.1002/hbm.24473 · Cited by 75 · see citing works
“symptoms of cognitive decline, which are directly caused by neurodegeneration, and tau accumulation happens in between the two (Jack et al., 2013; Quiroz et al., 2018).”
BackgroundInsights into Computational Drug Repurposing for Neurodegenerative Disease
Paranjpe, M. D., Taubes, A. L., & Sirota, M. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.06.003 · Cited by 71 · see citing works
Pan, S., Ding, A., Li, Y., Sun, Y., Zhan, Y., Ye, Z., Song, N., Peng, B., Li, L., Huang, W., et al. (2023) · Chemical Society Reviews · doi:10.1039/d3cs00056g · Cited by 71 · see citing works
d’Abramo, C., D'adamio, L., & Giliberto, L. (2020) · Journal of Personalized Medicine · doi:10.3390/jpm10030116 · Cited by 68 · see citing works
Translational approaches to understanding resilience to Alzheimer’s disease
Neuner, S. M., Telpoukhovskaia, M., Menon, V., O’Connell, K. M. S., Hohman, T. J., & Kaczorowski, C. C. (2022) · Trends in Neurosciences · doi:10.1016/j.tins.2022.02.005 · Cited by 68 · see citing works
“Carriers of the PSEN1 E280A mutation exhibit an average age of dementia onset at 49 years [21,22], so this individual seemed highly resilient to the typically deleterious effects of the mutation [20].”
BackgroundThe complex pathway between amyloid β and cognition: implications for therapy
Jagust, W. J., Teunissen, C. E., & DeCarli, C. S. (2023) · The Lancet Neurology · doi:10.1016/s1474-4422(23)00128-x · Cited by 63 · see citing works
Alzheimer's disease neuroimaging
Whitwell, J. L. (2018) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000570 · Cited by 64 · see citing works
Sanchez, J. S., Hanseeuw, B. J., Lopera, F., Sperling, R. A., Baena, A., Bocanegra, Y., Aguillon, D., Guzmán-Vélez, E., Pardilla-Delgado, E., Ramirez-Gomez, L., et al. (2021) · Alzheimer's Research & Therapy · doi:10.1186/s13195-020-00765-5 · Cited by 58 · see citing works
“EC tau levels were significantly elevated in all impaired carriers and in unimpaired carriers as early as 9 EYO— younger than we previously reported in this cohort [18].”
BackgroundResultSelf-citation(2019) · doi:10.14283/jpad.2019.6 · Cited by 57 · see citing works
“Flortaucipir PET imaging of tau in the brain of carriers has shown progressive accumulation of tau in the entorhinal cortex and inferior temporal lobe an average of -6 EYO, and an estimated 10 years after the first evidence of cortical Aβ1-42 (37).”
InfluentialSelf-citationBiphasic cortical macro‐ and microstructural changes in autosomal dominant Alzheimer's disease
Montal, V., Vilaplana, E., Pegueroles, J., Bejanin, A., Alcolea, D. A., Carmona‐Iragui, M., Clarimón, J., Levin, J., Cruchaga, C., Graff‐Radford, N. R., et al. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12224 · Cited by 56 · see citing works
“Thereafter, when comparing mutation carriers and non–carriers with EYO in the A+T CSF + phase, we did not see differences until the earliest reported alterations in tau PET, which occur 6 years before the symptoms onset 32 .”
BackgroundIaccarino, L., Joie, R. L., Edwards, L., Strom, A., Schonhaut, D. R., Ossenkoppele, R., Pham, J. Q., Mellinger, T. J., Janabi, M., Baker, S. L., et al. (2020) · Cerebral Cortex · doi:10.1093/cercor/bhaa184 · Cited by 55 · see citing works
Aguillon, D., Langella, S., Chen, Y., Sanchez, J. S., Su, Y., Vila‐Castelar, C., Vasquez, D., Zetterberg, H., Hansson, O., Dage, J. L., et al. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.12906 · Cited by 54 · see citing works
Self-citationAulston, B. D., Liu, Q., Mante, M., Florio, J. B., Rissman, R. A., & Yuan, S. H. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190656 · Cited by 54 · see citing works
“Early presymptomatic accumulations of Aβ are a signature of fAD [1].”
A multifactorial model of pathology for age of onset heterogeneity in familial Alzheimer’s disease
Sepulveda-Falla, D., Chavez-Gutierrez, L., Portelius, E., Vélez, J. I., Dujardin, S., Barrera-Ocampo, A., Dinkel, F., Hagel, C., Puig, B., Mastronardi, C., et al. (2021) · Acta Neuropathologica · doi:10.1007/s00401-020-02249-0 · Cited by 54 · see citing works
Self-citationGoing round in circles—The Papez circuit in Alzheimer's disease
Forno, G., Lladó, A., & Hornberger, M. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.15494 · Cited by 43 · see citing works
Trajectory of Unawareness of Memory Decline in Individuals With Autosomal Dominant Alzheimer Disease
Vannini, P., Hanseeuw, B. J., Gatchel, J. R., Sikkes, S. A. M., Alzate, D., Zuluaga, Y., Moreno, S., Méndez, L., Baena, A. Y., Ospina-Lopera, P., et al. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.27472 · Cited by 44 · see citing works
Self-citationPerdoncin, M., Konrad, A., Wyner, J. R., Lohana, S., Pillai, S. S., Pereira, D. G., Lakhani, H. V., & Sodhi, K. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.756499 · Cited by 38 · see citing works
Imaging of Tau Pathology in Neurodegenerative Diseases: An Update
Beyer, L., & Brendel, M. (2020) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2020.12.004 · Cited by 42 · see citing works
“In autosomal-dominant amyloid-positive AD mutation carriers and patients in presymptomatic stages, tracer retention was found in the medial temporal regions up to six years before clinical onset of cognitive impairment 55 56 .”
Norton, D. J., Parra, M. A., Sperling, R. A., Baena, A. Y., Guzmán‐Vélez, E., Jin, D. S., Andrea, N., Khang, J., Schultz, A. P., Rentz, D. M., et al. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00660-z · Cited by 40 · see citing works
Self-citationCorsetti, V., Borreca, A., Latina, V., Giacovazzo, G., Pignataro, A., Krashia, P., Natale, F., Cocco, S., Rinaudo, M., Malerba, F., et al. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa039 · Cited by 41 · see citing works
“…2004; Bolmont et al. , 2007) and that an enhanced neuropathology occurs following in vivo interaction between A b and tau (Gotz et al. , 2001; Lewis et al. , 2001; Hurtado et al. , 2010; Bennett et al. , 2017; Pontecorvo et al. , 2017; He et al. , 2018; Jacobs et al. , 2018; Quiroz et al. , 2018).”
Neuronal levels and sequence of tau modulate the power of brain rhythms
Das, M. M., Maeda, S., Hu, B., Yu, G.-Q., Guo, W., Lopez, I., Yu, X., Tai, C., Wang, X., & Mucke, L. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.05.020 · Cited by 41 · see citing works
Jacobs, H. I. L., Becker, J. A., Kwong, K. K., Munera, D., Ramirez-Gomez, L. A., Engels, N., Sanchez, J. S., Vila‐Castelar, C., Baena, A. Y., Sperling, R. A., et al. (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12656 · Cited by 41 · see citing works
Self-citationGhisays, V., Goradia, D. D., Protas, H. D., Bauer, R. J., III, Devadas, V., Tariot, P. N., Lowe, V. J., Knopman, D. S., Petersen, R. C., Jack, C. R., et al. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.08.195 · Cited by 35 · see citing works
Self-citationTesting the amyloid cascade hypothesis: Prevention trials in autosomal dominant Alzheimer disease
Levin, J., Vöglein, J., Quiroz, Y. T., Bateman, R. J., Ghisays, V., Lopera, F., McDade, E., Reiman, E., Tariot, P. N., & Morris, J. C. (2022) · Alzheimer's & Dementia · doi:10.1002/alz.12624 · Cited by 40 · see citing works
Self-citationLlibre‐Guerra, J. J., Li, Y., Schindler, S. E., Gordon, B. A., Fagan, A. M., Morris, J. C., Benzinger, T. L. S., Hassenstab, J. J., Wang, G., Allegri, R., et al. (2019) · JAMA Network Open · doi:10.1001/jamanetworkopen.2019.17126 · Cited by 38 · see citing works
Aluminum and Tau in Neurofibrillary Tangles in Familial Alzheimer’s Disease
Mold, M. J., O’Farrell, A., Morris, B., & Exley, C. (2021) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-210011 · Cited by 39 · see citing works
“As a consequence of the late onset of tau pathology in the PSEN1-E280A brain, such may account for the early and widespread distribution of NFTs in the temporal cortex and perhaps their association with aluminum [35, 36].”
BackgroundInfluentialBarthélemy, N. R., Toth, B., Manser, P. T., Sanabria-Bohórquez, S., Teng, E., Keeley, M., Bateman, R. J., Weimer, R. M., & Wildsmith, K. R. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210677 · Cited by 33 · see citing works
“CSF total tau (t-tau) and phosphorylated tau (p-tau) levels, which reflect the circulating pool of soluble tau released by central nervous system cells [17], may enable earlier assessment of tau abnormalities prior to the deposition of NFTs in brain parenchyma [18, 19].”
BackgroundWisch, J. K., McKay, N. S., Boerwinkle, A. H., Kennedy, J., Flores, S., Handen, B. L., Christian, B. T., Head, E., Mapstone, M., Rafii, M. S., et al. (2024) · The Lancet Neurology · doi:10.1016/s1474-4422(24)00084-x · Cited by 37 · see citing works
“8 In people with Down syndrome, amyloid accumulates about 17 years before symptom onset, 2 and evidence suggests that tau might begin to accumulate before people with Down syndrome become amyloid positive.”
Self-citationMiR-29c-3p May Promote the Progression of Alzheimer’s Disease through BACE1
Cao, Y., Tan, X., Lu, Q., Huang, K., Tang, X.-E., & He, Z. (2021) · Journal of Healthcare Engineering · doi:10.1155/2021/2031407 · Cited by 36 · see citing works
Pathological Alterations of Tau in Alzheimer’s Disease and 3xTg-AD Mouse Brains
Li, L., Jiang, Y., Hu, W. H., Tung, Y. C., Dai, C., Chu, D., Gong, C., Iqbal, K., & Liu, F. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-1507-4 · Cited by 35 · see citing works
Fessel, J. (2019) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2019.09.019 · Cited by 37 · see citing works
“Dementia appears at an average age of 49 years but brain imaging of their brains shows amyloid 15 years before and tau deposition 6 years before the dementia [3].”
BackgroundZeng, P. H., Su, H.-F., Ye, C., Qiu, S.-W., Shi, A., Wang, J., Zhou, X., & Tian, Q. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.877806 · Cited by 33 · see citing works
“Notably, deposition of tau was evident many years before clinical symptoms appeared (Quiroz et al., 2018), and the extent of tau lesions in the brain has been shown to be closely related to the severity of dementia in AD patients (Braak and Braak, 1991).”
BackgroundStriatal amyloid is associated with tauopathy and memory decline in familial Alzheimer’s disease
Hanseeuw, B. J., Lopera, F. J., Sperling, R. A., Norton, D. J., Guzmán‐Vélez, E., Baena, A. Y., Pardilla‐Delgado, E., Schultz, A. P., Gatchel, J. R., Jin, D. S., et al. (2019) · Alzheimer s Research & Therapy · doi:10.1186/s13195-019-0468-1 · Cited by 30 · see citing works
“FTP-SUVRs were characterized in the entorhinal cortex ROI, since this region was found to be associated with early FTP-SUVR increases over age in our PSEN1-E280A kindred [3].”
InfluentialSelf-citationBiomarkers of neurodegeneration across the Global South
McGlinchey, E., Duran-Aniotz, C., Akinyemi, R., Arshad, F., Zimmer, E. R., Cho, H., Adewale, B. A., & Ibanez, A. (2024) · The Lancet Healthy Longevity · doi:10.1016/s2666-7568(24)00132-6 · Cited by 32 · see citing works
Role of tau deposition in early cognitive decline in Down syndrome
Hartley, S. L., Handen, B. L., Tudorascu, D., Lee, L., Cohen, A. D., Piro‐Gambetti, B., Zammit, M. D., Klunk, W. E., Laymon, C. M., Zaman, S. H., et al. (2022) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12256 · Cited by 31 · see citing works
Discontinued disease-modifying therapies for Alzheimer’s disease: status and future perspectives
Imbimbo, B. P., Lozupone, M., Watling, M., & Panza, F. (2020) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2020.1795127 · Cited by 31 · see citing works
Soto‐Mercado, V., Mendivil‐Perez, M., Velez‐Pardo, C., Lopera, F. J., & Jiménez-Del-Río, M. (2020) · PLoS ONE · doi:10.1371/journal.pone.0221669 · Cited by 33 · see citing works
“Similar to the majority of dominant-negative PSEN1 mutations [15, 16], PSEN1 E280A produces increased Aβ42 deposition [17], hippocampal neuron loss [18], and Aβ/TAU accumulation in young adults [19, 20].”
BackgroundSelf-citationGenetic origin of a large family with a novel PSEN1 mutation (Ile416Thr)
Aguilar, L. R., Acosta‐Uribe, J., Giraldo, M., Moreno, S., Baena, A. Y., Alzate, D., Cuastumal, A. R., Aguillon, D. F., Madrigal, L., Saldarriaga, A., et al. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2018.12.010 · Cited by 32 · see citing works
“11C Pittsburgh compound B PET data were expressed as the distribution volume ratio with cerebellar gray as reference tissue, using a large cortical Region of Interest aggregate that included frontal, lateral temporal, and retrosplenial cortices as described previously [23].”
BackgroundMethodResultSelf-citationMold, M. J., O’Farrell, A., Morris, B., & Exley, C. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200838 · Cited by 29 · see citing works
“Donors from the Colombian PSEN1-E280A fAD cohort are known to develop tauopathies later in life, as has been demonstrated by positron emission tomography (PET), in living patients [55].”
BackgroundGhisays, V., Lopera, F. J., Goradia, D. D., Protas, H. D., Malek‐Ahmadi, M. H., Chen, Y., Devadas, V., Luo, J., Lee, W., Baena, A. Y., et al. (2021) · NeuroImage Clinical · doi:10.1016/j.nicl.2021.102749 · Cited by 28 · see citing works
“Cognitive assessments were done within 1–3 months of the brain scans for the API ADAD cohort and two months for the COLBOS cohort (Quiroz et al., 2018).”
InfluentialSelf-citationLlibre‐Guerra, J. J., Li, Y., Allegri, R., Méndez, P. C., Surace, E. I., Rodríguez, J. J. L., Sosa, A. L., Aláez‐Verson, C., Longoria-Ibarrola, E. M., Téllez‐Martínez, J. A., et al. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12227 · Cited by 29 · see citing works
Self-citationPerez-Corredor, P., Vanderleest, T. E., Vacano, G. N., Sanchez, J. S., Villalba-Moreno, N. D., Marino, C., Krasemann, S., Mendivil-Perez, M. A., Aguillón, D., Jiménez-Del-Río, M., et al. (2024) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2024.1373568 · Cited by 28 · see citing works
Self-citationPanza, F., Dibello, V., Sardone, R., Zupo, R., Castellana, F., Leccisotti, I., Moretti, M. C., Altamura, M., Bellomo, A., Daniele, A., et al. (2025) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2025.2463963 · Cited by 27 · see citing works
“…form or ADAD is caused by mutations in the genes coding for the amyloid precursor protein (APP), the precursor of Aβ peptide, or in the genes coding for presenilin 1 and 2 (PSEN1 and PSEN2), protease enzymes directly regulating the γ-secretase enzyme complex, cleaving the Aβ peptide from APP [5].”
Guzmán‐Vélez, E., Zetterberg, H., Fox‐Fuller, J. T., Vila‐Castelar, C., Sanchez, J. S., Baena, A. Y., Garcia‐Ospina, G., Aguillon, D. F., Pardilla‐Delgado, E., Gatchel, J. R., et al. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12248 · Cited by 24 · see citing works
Self-citationBurnham, S. C., Iaccarino, L., Pontecorvo, M. J., Fleisher, A., Lu, M., Collins, E. C., & Devous, M. D. (2023) · Brain Communications · doi:10.1093/braincomms/fcad305 · Cited by 29 · see citing works
de la Torre, J. C. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201165 · Cited by 26 · see citing works
“These findings essentially reveal that the formation ofA (cid:2) peptideaccumulationinthebrainisalateevent, unlikely to be the primary cause of AD [2, 47, 51], or that its accumulation triggers or precedes NFTs, as previously argued in the amyloid cascade hypothesis [45, 47, 52, 53].”
Critical thinking on amyloid-beta-targeted therapy: challenges and perspectives
Sun, B., Chen, Y., Fan, D., Zhu, C., Zeng, F., & Wang, Y. (2020) · Science China Life Sciences · doi:10.1007/s11427-020-1810-y · Cited by 25 · see citing works
An Alzheimer’s-disease-protective APOE mutation
Zalocusky, K. A., Nelson, M. R., & Huang, Y. (2019) · Nature Medicine · doi:10.1038/s41591-019-0634-9 · Cited by 25 · see citing works
Early molecular events of autosomal‐dominant Alzheimer's disease in marmosets with PSEN1 mutations
Homanics, G. E., Park, J. E., Bailey, L. S., Schaeffer, D. J., Schaeffer, L. K. H., He, J., Li, S., Zhang, T., Haber, A., Spruce, C. A., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13806 · Cited by 20 · see citing works
Targeting Mitophagy in Alzheimer’s Disease
Jayatunga, D. P. W., Hone, E., Bharadwaj, P., Garg, M. L., Verdile, G., Guillemin, G. J., & Martins, R. N. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-191258 · Cited by 24 · see citing works
Tau Positron Emission Tomography in Autosomal Dominant Alzheimer Disease
McDade, E., & Bateman, R. J. (2018) · JAMA Neurology · doi:10.1001/jamaneurol.2017.4026 · Cited by 22 · see citing works
Vila‐Castelar, C., Guzmán‐Vélez, E., Pardilla‐Delgado, E., Buckley, R. F., Bocanegra, Y., Baena, A. Y., Fox‐Fuller, J. T., Tirado, V., Muñoz, C., Giraldo, M., et al. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200723 · Cited by 20 · see citing works
“…mutation carriers, with elevated cortical amyloid accumulation 15 years before clinical symptom onset (i.e., mild cognitive impairment) and elevated levels of tau in medial temporal lobe regions (i.e., entorhinal cortex and inferior temporal lobe) 6 years before clinical symptom onset [17, 20, 21].”
Self-citationNi, Y., Kong, L., Li, X., et al. (2020) · Journal of Liposome Research · doi:10.1080/08982104.2020.1806872 · Cited by 21 · see citing works
“…0.05, p< 0.05, ^^p< 0.01. determine the pharmacokinetic parameters of the drug in vivo, but also provide the drug concentration data for pharmacodynamics and toxicology evaluations, and provide the basis for optimising the dosage regimen in clinical research (Quiroz et al. 2018; Wei et al. 2019).”
BackgroundInfluentialPioneering Alzheimer’s study in Colombia zeroes in on enigmatic protein
Reardon, S. (2018) · Nature · doi:10.1038/d41586-018-03848-4 · Cited by 21 · see citing works
An Overview of Experimental and Clinical Spinal Cord Findings in Alzheimer’s Disease
Xie, Q., Zhao, W., Ou, G., & Xue, W. (2019) · Brain Sciences · doi:10.3390/brainsci9070168 · Cited by 20 · see citing works
“These pathological features not only occur in brain tissue but also involve the spinal cord (Figure 2) [58,59].”
BackgroundVila‐Castelar, C., Muñoz, N., Papp, K. V., Amariglio, R. E., Baena, A. Y., Guzmán‐Vélez, E., Bocanegra, Y., Sanchez, J. S., Reiman, E. M., Johnson, K. A., et al. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00671-w · Cited by 18 · see citing works
Self-citationCiarmiello, A., Giovannini, E., Riondato, M., Giovacchini, G., Duce, V., Ferrando, O., Biasi, M. D., Passera, C., Carabelli, E., Mannironi, A., et al. (2019) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-019-04409-1 · Cited by 19 · see citing works
Li, L., Miao, J., Chu, D., Jin, N., Tung, Y. C., Dai, C., Hu, W. H., Gong, C., Iqbal, K., & Liu, F. (2022) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13970 · Cited by 17 · see citing works
Ramirez-Gomez, L. A., Albers, M. W., Baena, A. Y., Vila‐Castelar, C., Fox‐Fuller, J. T., Sanchez, J. S., Jain, F. A., Albers, A. D., Lopera, F. J., & Quiroz, Y. T. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220075 · Cited by 15 · see citing works
Self-citationSoto‐Mercado, V., Mendivil‐Perez, M., Velez‐Pardo, C., & Jiménez-Del-Río, M. (2021) · Biomolecules · doi:10.3390/biom11121845 · Cited by 18 · see citing works
“, [13,14]), there are no efficient therapies to date.”
BackgroundArmstrong, G. W., Kim, L. A., Vingopoulos, F., Park, J. Y., Garg, I., Kasetty, M. A., Silverman, R. F., Zeng, R., Douglas, V. P., Lopera, F. J., et al. (2020) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2020.4909 · Cited by 17 · see citing works
Self-citationAccelerating Alzheimer’s disease drug discovery and development: what’s the way forward?
Imbimbo, B. P., Ippati, S., Watling, M. I. L., & Balducci, C. (2021) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2021.1887132 · Cited by 17 · see citing works
“and biomarker features that are similar to those of SAD and usually occurs at a younger age [2], but can also emerge at later ages [3].”
BackgroundSoto‐Mercado, V., Mendivil‐Perez, M., Jiménez-Del-Río, M., & Velez‐Pardo, C. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-201045 · Cited by 18 · see citing works
“As the majority of dominant-negative PSEN1 mutations [11], PSEN1 E280A produces increased A 42 deposition [12], hippocampal neuron loss [13], and A /tau accumulation in young adults [14, 15].”
BackgroundMendivil‐Perez, M., Velez‐Pardo, C., Kosik, K. S., Lopera, F. J., & Jiménez-Del-Río, M. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.03.032 · Cited by 15 · see citing works
Self-citationIn vivo Brainstem Imaging in Alzheimer’s Disease: Potential for Biomarker Development
Braun, D. J., & Eldik, L. J. V. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00266 · Cited by 15 · see citing works
“It can also measure functional parameters relevant to AD pathology such as tissue perfusion (Wolk and Detre, 2012) or blood brain barrier (BBB) integrity (Raja et al., 2017); however, these methods have yet to be validated for biomarker use.”
Background
- 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
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › 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
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