A multicentre longitudinal study of flortaucipir (18F) in normal ageing, mild cognitive impairment and Alzheimer’s disease dementia

Pontecorvo, Michael J.; Devous, Michael D.; Kennedy, Ian; Navitsky, Michael; Lu, Ming; Galante, Nicholas; Salloway, Stephen; Doraiswamy, P. Murali; Southekal, Sudeepti; Arora, Ankit; McGeehan, Anne; Lim, Nathaniel; Xiong, Hui; Truocchio, Stephen P; Joshi, Abhinay D.; Shcherbinin, Sergey; Teske, Brian F.; Fleisher, Adam; Mintun, Mark A.

doi:10.1093/brain/awz090

Cited by 167 publications

(234 citation statements)

References 75 publications

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“…Another study of longitudinal tau accumulation showed increases in 18 F-AV-1451 retention over 1-3 years in temporal and medial parietal areas in healthy older adults [39]. These findings were further expanded on by a recent study reporting that individuals with baseline 18 F-AV-1451 SUVRs in the second quartile exhibited tau tracer retention increases in inferior and lateral temporal cortex and in posterior cingulate over 18 months [15]. Men in our sample had higher 18 F-AV-1451 SUVR than women, mainly in frontal and parietal white matter and thalamus.…”

Section: Discussionmentioning

confidence: 85%

“…Lower hippocampal volume has also been associated with greater tau radiotracer retention in the hippocampus [8,10]. Longitudinal studies including individuals ranging from CN to demented have further found that higher baseline tau tracer retention is associated with greater rates of brain volume loss [11,12] and global cognitive decline [13–15].…”

Section: Introductionmentioning

confidence: 99%

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Tau pathology in cognitively normal older adults

Ziontz

Bilgel

Shafer

et al. 2019

Alz & Dem Diag Ass & Dis Mo

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Introduction Tau pathology, a hallmark of Alzheimer's disease, is observed in the brains of virtually all individuals over 70 years. Methods Using 18 F-AV-1451 ( 18 F-flortaucipir) positron emission tomography, we evaluated tau pathology in 54 cognitively normal participants (mean age: 77.5 years, SD: 8.9) from the Baltimore Longitudinal Study of Aging. We assessed associations between positron emission tomography signal and age, sex, race, and amyloid positivity. We investigated relationships between regional signal and retrospective rates of change in regional volumes and cognitive function adjusting for age, sex, and amyloid status. Results Greater age, male sex, black race, and amyloid positivity were associated with higher 18 F-AV-1451 retention in distinct brain regions. Retention in the entorhinal cortex was associated with lower entorhinal volume ( β = −1.124, SE = 0.485, P = .025) and a steeper decline in memory performance ( β = −0.086, SE = 0.039, P = .029). Discussion Assessment of medial temporal tau pathology will provide insights into early structural brain changes associated with later cognitive impairment and Alzheimer's disease.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Tau pathology in cognitively normal older adults

Ziontz

Bilgel

Shafer

et al. 2019

Alz & Dem Diag Ass & Dis Mo

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“…Congruent with this result pattern, previous studies have shown that longitudinal AV1451 tau-PET changes can be detected in ROI based analyses without partial-volume correction, where partial-volume correction simply increases the sensitivity for detecting AV1451 tau-PET changes 27 . Similarly, recent studies using voxel-wise approaches have also reported significant tau accumulation in both aging and AD in nonpartial volumecorrected tau-PET data 46,47 . Together, partial-volume correction may enhance the sensitivity to detect tau-PET changes, but tau-PET changes can also be detected without partial-volume correction.…”

Section: Discussionmentioning

confidence: 87%

Functional brain architecture is associated with the rate of tau accumulation in Alzheimer’s disease

2020

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In Alzheimer's diseases (AD), tau pathology is strongly associated with cognitive decline. Preclinical evidence suggests that tau spreads across connected neurons in an activitydependent manner. Supporting this, cross-sectional AD studies show that tau deposition patterns resemble functional brain networks. However, whether higher functional connectivity is associated with higher rates of tau accumulation is unclear. Here, we combine resting-state fMRI with longitudinal tau-PET in two independent samples including 53 (ADNI) and 41 (BioFINDER) amyloid-biomarker defined AD subjects and 28 (ADNI) vs. 16 (Bio-FINDER) amyloid-negative healthy controls. In both samples, AD subjects show faster tau accumulation than controls. Second, in AD, higher fMRI-assessed connectivity between 400 regions of interest (ROIs) is associated with correlated tau-PET accumulation in corresponding ROIs. Third, we show that a model including baseline connectivity and tau-PET is associated with future tau-PET accumulation. Together, connectivity is associated with tau spread in AD, supporting the view of transneuronal tau propagation.

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“…Amyvid ([ 18 F]AV‐45, [ 18 F] 5 ) was the first amyloid‐β PET imaging agent approved by the FDA in 2012. It is now available for routine clinical use in assisting diagnosis of patients suspected of Alzheimer disease (AD) and also for selecting patients in drug trials . Florbetapir f18 PET imaging study is now being used to determine the presence of amyloid load in the brain as a significant risk factor for developing AD.…”

Section: Introductionmentioning

confidence: 99%

“…It is now available for routine clinical use in assisting diagnosis of patients suspected of Alzheimer disease (AD) and also for selecting patients in drug trials. [6][7][8][9][10] Florbetapir f18 PET imaging study is now being used to determine the presence of amyloid load in the brain as a significant risk factor for developing AD. Amyloidβ plaques in the brain are associated with mild cognitive impairment or dementia of uncertain etiology.…”

Section: Introductionmentioning

confidence: 99%

An improved preparation of [¹⁸F]AV‐45 by simplified solid‐phase extraction purification

Zhang

Yao

et al. 2020

Labelled Comp Radiopharmac

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Amyvid (florbetapir f18, [18F]AV‐45, [18F]5) was the first FDA‐approved positron emission tomography imaging agent targeting β‐amyloid (Aβ) plaques for assisting the diagnosis of Alzheimer disease. This work aimed to improve the [18F]AV‐45 ([18F]5) preparation by using solid‐phase extraction (SPE) purification. [18F]AV‐45 ([18F]5) was synthesized by direct nucleophilic radiofluorination of O‐tosylated precursor (1 mg) at 120°C in anhydrous dimethyl sulfoxide (DMSO), followed by acid hydrolysis of the N‐Boc protecting group. Purification was accomplished by loading the crude reaction mixture to a cartridge (Oasis HLB 3 cc) and eluting with different combinations of solvents. This method removed the chemical impurity while leaving [18F]AV‐45 ([18F]5) on the cartridge. The final dose was eluted by ethanol. [18F]AV‐45 ([18F]5) was produced within 51 minutes (radiochemical yield 42.7 ± 5.9%, decay corrected, n = 3), and the radiochemical purity was greater than 95%. Total chemical impurity per batch (24.1 ± 2.7 μg per batch) was below the limit described in the package insert of Amyvid, florbetapir f18 (chemical mass: less than 50 μg/dose). In summary, [18F]AV‐45 ([18F]5) was produced efficiently and reproducibly using a cartridge‐based SPE purification. This method brings the process closer for routine preparation, similar to the commercially used [18F]FDG.

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A multicentre longitudinal study of flortaucipir (18F) in normal ageing, mild cognitive impairment and Alzheimer’s disease dementia

Cited by 167 publications

References 75 publications

Tau pathology in cognitively normal older adults

Tau pathology in cognitively normal older adults

Functional brain architecture is associated with the rate of tau accumulation in Alzheimer’s disease

An improved preparation of [¹⁸F]AV‐45 by simplified solid‐phase extraction purification

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A multicentre longitudinal study of flortaucipir (18F) in normal ageing, mild cognitive impairment and Alzheimer’s disease dementia

Cited by 167 publications

References 75 publications

Tau pathology in cognitively normal older adults

Tau pathology in cognitively normal older adults

Functional brain architecture is associated with the rate of tau accumulation in Alzheimer’s disease

An improved preparation of [18F]AV‐45 by simplified solid‐phase extraction purification

Contact Info

Product

Resources

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An improved preparation of [¹⁸F]AV‐45 by simplified solid‐phase extraction purification