Associations between [
            <sup>18</sup>
            F]AV1451 tau PET and CSF measures of tau pathology in a clinical sample

Joie, Renaud La; Bejanin, Alexandre; Fagan, Anne M.; Ayakta, Nagehan; Baker, Suzanne L.; Bourakova, Viktoriya; Boxer, Adam L.; Cha, Jung-Ho; Karydas, Anna; Jerome, Gina M.; Maaß, Anne; Mensing, Ashley; Miller, Zachary A.; O’Neil, James P.; Pham, Julie; Rosen, Howard J.; Tsai, Richard; Visani, Adrienne; Miller, Bruce L.; Jagust, William J.; Rabinovici, Gil D.

doi:10.1212/wnl.0000000000004860

Cited by 127 publications

(123 citation statements)

References 38 publications

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“…did not evaluate age of onset by APOE ε4 alleles, it is possible that APOE ε4 may increase overall risk of LBD, but not accelerate age of onset, although a mechanism for this association remains unclear. Their inclusion of NFTs within the occipital‐temporal gyrus, rhinal sulcus, and entorhinal region (ie, Braak Stage III) in their sample may have influenced findings as APOE ε4 has been associated with tau deposition and distribution . Thus, it is possible that their findings were associated with tau versus Lewy pathology.…”

Section: Discussionmentioning

confidence: 96%

“…20 In contrast, APOE 4 did not appear to hasten onset in the pure LBD group, despite previous research suggesting APOE 4 increases risk of dementia in autopsyconfirmed LBD. 21 In a study by Tsuang et al, 21 22 Thus, it is possible that their findings were associated with tau versus Lewy pathology. Additionally, few homozygous APOE 4 carriers in our LBD group, which is more associated with dementia risk, may have reduced power.…”

Section: Discussionmentioning

confidence: 99%

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Risk factors for earlier dementia onset in autopsy‐confirmed Alzheimer's disease, mixed Alzheimer's with Lewy bodies, and pure Lewy body disease

Schaffert

LoBue

White

et al. 2020

Alzheimer's & Dementia

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Introduction Clinical Alzheimer's disease (AD) and dementia with Lewy bodies often have mixed AD and Lewy pathology, making it difficult to delineate risk factors. Methods Six risk factors for earlier dementia onset due to autopsy‐confirmed AD (n = 647), mixed AD and Lewy body disease (AD + LBD; n = 221), and LBD (n = 63) were entered into multiple linear regressions using data from the National Alzheimer's Coordinating Center. Results In AD and AD + LBD, male sex and apolipoprotein E (APOE) ɛ4 alleles each predicted a 2‐ to 3‐year‐earlier onset and depression predicted a 3‐year‐earlier onset. In LBD, higher education predicted earlier onset and depression predicted a 5.5‐year‐earlier onset. Discussion Male sex and APOE ɛ4 alleles increase risk for earlier dementia onset in AD but not LBD. Depression increases risk for earlier dementia onset in AD, LBD, and AD + LBD, but evaluating the course, treatment, and severity is needed in future studies.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Risk factors for earlier dementia onset in autopsy‐confirmed Alzheimer's disease, mixed Alzheimer's with Lewy bodies, and pure Lewy body disease

Schaffert

LoBue

White

et al. 2020

Alzheimer's & Dementia

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“…An initial study pointed toward better discriminative accuracy for [ 18 F]flortaucipir PET compared with CSF tau in mild-to-moderate AD, 35 while another found equivalent performance for discriminating AD from non-AD neurodegenerative disorders. 36 The superior performance of [ 18 F]flortaucipir compared with established MRI markers suggests that [ 18 F]flortaucipir could precede structural MRI when the differential diagnosis includes AD dementia. In case of a negative [ 18 F]flortaucipir scan, the atrophy pattern might help determine the type of non-AD dementia.…”

Section: Discussionmentioning

confidence: 99%

Discriminative Accuracy of [¹⁸F]flortaucipir Positron Emission Tomography for Alzheimer Disease vs Other Neurodegenerative Disorders

Ossenkoppele

Rabinovici

Smith

et al. 2018

JAMA

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334

415

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IMPORTANCE The positron emission tomography (PET) tracer [ 18 F]flortaucipir allows in vivo quantification of paired helical filament tau, a core neuropathological feature of Alzheimer disease (AD), but its diagnostic utility is unclear. OBJECTIVE To examine the discriminative accuracy of [ 18 F]flortaucipir for AD vs non-AD neurodegenerative disorders. DESIGN, SETTING, AND PARTICIPANTS In this cross-sectional study, 719 participants were recruited from 3 dementia centers in South Korea, Sweden, and the United States between June 2014 and November 2017 (160 cognitively normal controls, 126 patients with mild cognitive impairment [MCI], of whom 65.9% were amyloid-β [Aβ] positive [ie, MCI due to AD], 179 patients with AD dementia, and 254 patients with various non-AD neurodegenerative disorders).EXPOSURES The index test was the [ 18 F]flortaucipir PET standardized uptake value ratio (SUVR) in 5 predefined regions of interest (ROIs). Cut points for tau positivity were determined using the mean +2 SDs observed in controls and Youden Index for the contrast AD dementia vs controls. MAIN OUTCOMES AND MEASURESThe reference standard was the clinical diagnosis determined at the specialized memory centers. In the primary analysis, the discriminative accuracy (ie, sensitivity and specificity) of [ 18 F]flortaucipir was examined for AD dementia vs all non-AD neurodegenerative disorders. In secondary analyses, the area under the curve (AUC) of [ 18 F]flortaucipir SUVR was compared with 3 established magnetic resonance imaging measures (hippocampal volumes and AD signature and whole-brain cortical thickness), and sensitivity and specificity of [ 18 F]flortaucipir in MCI due to AD vs non-AD neurodegenerative disorders were determined. RESULTS Among 719 participants, the overall mean (SD) age was 68.8 (9.2) years and 48.4% were male. The proportions of patients who were amyloid-β positive were 26.3%, 65.9%, 100%, and 23.8% among cognitively normal controls, patients with MCI, patients with AD dementia, and patients with non-AD neurodegenerative disorders, respectively. [ 18 F]flortaucipir uptake in the medial-basal and lateral temporal cortex showed 89.9% (95% CI, 84.6%-93.9%) sensitivity and 90.6% (95% CI, 86.3%-93.9%) specificity using the threshold based on controls (SUVR, 1.34), and 96.8% (95% CI, 92.0%-99.1%) sensitivity and 87.9% (95% CI, 81.9%-92.4%) specificity using the Youden Index-derived cutoff (SUVR, 1.27) for distinguishing AD dementia from all non-AD neurodegenerative disorders. The AUCs for all 5 [ 18 F]flortaucipir ROIs were higher (AUC range, 0.92-0.95) compared with the 3 volumetric MRI measures (AUC range, 0.63-0.75; all ROIs P < .001). Diagnostic performance of the 5 [ 18 F]flortaucipir ROIs were lower in MCI due to AD (AUC range, 0.75-0.84).CONCLUSIONS AND RELEVANCE Among patients with established diagnoses at a memory disorder clinic, [ 18 F]flortaucipir PET was able to discriminate AD from other neurodegenerative diseases. The accuracy and potential utility of this test in patient care require further rese...

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“…To measure tau pathology in vivo, we used CSF and PET measurements. Previous studies have demonstrated associations between CSF p-tau and tau-PET uptake in Alzheimer's disease-related brain regions [29][30][31]. The primary outcome measure of the study was tau pathology as measured by voxel-wise [ 18 F]MK6240 SUVR (TRIAD cohort), [ 18 F]Flortaucipir SUVR (ADNI tau-PET cohort), and CSF phosphorylated tau (ADNI CSF cohort).…”

Section: Statistical Analysesmentioning

confidence: 99%

APOEε4 potentiates the relationship between amyloid-β and tau pathologies

et al. 2020

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APOEε4 is the most well-established genetic risk factor for sporadic Alzheimer's disease and is associated with cerebral amyloid-β. However, the association between APOEε4 and tau pathology, the other major proteinopathy of Alzheimer's disease, has been controversial. Here, we sought to determine whether the relationship between APOEε4 and tau pathology is determined by local interactions with amyloid-β. We examined three independent samples of cognitively unimpaired, mild cognitive impairment and Alzheimer's disease subjects: (1) 211 participants who underwent tau-PET with [ 18 F]MK6240 and amyloid-PET with [ 18 F] AZD4694, (2) 264 individuals who underwent tau-PET with [ 18 F]Flortaucipir and amyloid-PET with [ 18 F]Florbetapir and (3) 487 individuals who underwent lumbar puncture and amyloid-PET with [ 18 F]Florbetapir. Using a novel analytical framework, we applied voxel-wise regression models to assess the interactive effect of APOEε4 and amyloid-β on tau load, independently of age and clinical diagnosis. We found that the interaction effect between APOEε4 and amyloid-β, rather than the sum of their independent effects, was related to increased tau load in Alzheimer's disease-vulnerable regions. The interaction between one APOEε4 allele and amyloid-β was related to increased tau load, while the interaction between amyloid-β and two APOEε4 alleles was related to a more widespread pattern of tau aggregation. Our results contribute to an emerging framework in which the elevated risk of developing dementia conferred by APOEε4 genotype involves mechanisms associated with both amyloid-β and tau aggregation. These results may have implications for future disease-modifying therapeutic trials targeting amyloid or tau pathologies.

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Associations between [ ¹⁸ F]AV1451 tau PET and CSF measures of tau pathology in a clinical sample

Abstract: This study provides Class III evidence that, in a clinical sample of patients with a variety of suspected neurodegenerative diseases, both CSF p-tau and [F]AV1451 distinguish AD from non-AD conditions.

Cited by 127 publications

References 38 publications

Risk factors for earlier dementia onset in autopsy‐confirmed Alzheimer's disease, mixed Alzheimer's with Lewy bodies, and pure Lewy body disease

Risk factors for earlier dementia onset in autopsy‐confirmed Alzheimer's disease, mixed Alzheimer's with Lewy bodies, and pure Lewy body disease

Discriminative Accuracy of [¹⁸F]flortaucipir Positron Emission Tomography for Alzheimer Disease vs Other Neurodegenerative Disorders

APOEε4 potentiates the relationship between amyloid-β and tau pathologies

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Associations between [ 18 F]AV1451 tau PET and CSF measures of tau pathology in a clinical sample

Abstract: This study provides Class III evidence that, in a clinical sample of patients with a variety of suspected neurodegenerative diseases, both CSF p-tau and [F]AV1451 distinguish AD from non-AD conditions.

Cited by 127 publications

References 38 publications

Risk factors for earlier dementia onset in autopsy‐confirmed Alzheimer's disease, mixed Alzheimer's with Lewy bodies, and pure Lewy body disease

Risk factors for earlier dementia onset in autopsy‐confirmed Alzheimer's disease, mixed Alzheimer's with Lewy bodies, and pure Lewy body disease

Discriminative Accuracy of [18F]flortaucipir Positron Emission Tomography for Alzheimer Disease vs Other Neurodegenerative Disorders

APOEε4 potentiates the relationship between amyloid-β and tau pathologies

Contact Info

Product

Resources

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Associations between [ ¹⁸ F]AV1451 tau PET and CSF measures of tau pathology in a clinical sample

Discriminative Accuracy of [¹⁸F]flortaucipir Positron Emission Tomography for Alzheimer Disease vs Other Neurodegenerative Disorders