Longitudinal multicenter head-to-head harmonization of TAU pet tracers

Active Project Grant Awarded Last action

Award ID
R01AG073267
Recipient
Awarding agency
Obligated
$92,109,982

Award facts

Assistance listing
93.866 Aging Research
Completion date 89% complete
Originally
Funding
  • $74,421,072.00 Federal
  • $17,688,910.00 Non-federal
Place of performance
Pittsburgh, PA 15222, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
The development of TAU positron emission tomography (pet) tracers has yielded the opportunity to better understand the TAU accumulation associated with the development of alzheimer's disease (ad), improve the diagnostic accuracy of ad, and test the effects of therapeutic interventions in TAU deposition. Our group and others have shown that [18F]flortaucipir has distribution patterns similar to those reported in postmortem studies and shows significant rates of TAU accumulation over time despite brain off-target signal in white matter, basal ganglia, and choroid plexus. [18F]MK-6240, a second-generation TAU tracer, has ~6-fold greater affinity for TAU tangles than [18F]flortaucipir and negligible brain off-target signal. However, [18F]MK-6240 has off-target uptake in the meninges adjacent to the entire cortex, which can compromise the signal within brain regions. We have shown that [18F]MK-6240 has similar patterns of uptake as postmortem and [18F]flortaucipir studies. However, [18F]MK-6240 has a higher dynamic range and, although measured in different cohorts, the annual change in TAU using [18F]MK-6240 appears to be greater than changes measured using [18F]flortaucipir. To date, more than 95% of sites in the US performing TAU pet studies are using one of these tracers. Although both tracers offer robust TAU estimates, these large differences in binding characteristics between them can lead to misleading interpretations of their outcomes and preclude the merging of their datasets using simple conversion methods. Thus, a well-powered longitudinal study assessing head-to-head [18F]flortaucipir and [18F]MK-6240 scans has the potential to: (1) standardize their analysis, allowing datasets to be combined, (2) compare their rates of longitudinal deposition to elucidate their advantages and limitations for research, trials, and practice, and (3) produce a benchmark dataset to be used by the scientific community to develop methods for pet quantification and harmonization. Here, we propose a multi-site longitudinal study in which 620 subjects (40 young controls, 280 cognitively unimpaired elderly, 200 mild cognitive impairment, 100 ad dementia) will receive [18F]flortaucipir and [18F]MK6240 scans at baseline and 18 months later. At each time point, subjects will also have an amyloid- SS (ASS) pet scan, magnetic resonance imaging, cognitive tests, and a blood draw for plasma TAU analyses. Methods will be harmonized with adni and the adrc program. In aim 1, we will (1) standardize processing methods, (2) convert to a common scale, (3) compare associations with ASS, atrophy, and cognition, and (4) compare braak staging between TAU tracers using cross-sectional data. In aim 2, we will (1) ascertain the optimal processing method for longitudinal analysis and (2) compare longitudinal accumulation between TAU tracers and its associations with changes in ASS, atrophy, and cognition. As recent results from our group and others have shown that the new p-TAU plasma assays identify brain TAU pathology, in exploratory aim 3, we will compare cross-sectional and longitudinal [18F]flortaucipir and [18F]MK6240 estimates with plasma p-TAU outcomes.

Transactions

Action Federal Non-federal Date
Amendment $0 $0
Amendment $179,928 $0
Amendment $1,151,010 $0
Amendment $179,928 $0
Amendment $1,151,010 $0
Amendment $5,532,594 $0
Amendment $5,532,594 $0
Amendment $7,801,112 $0
Amendment $8,757,538 $0
Amendment $8,757,538 $0
Amendment $8,941,002 $0
Amendment $8,941,002 $8,941,002
Amendment $8,747,908 $0
Original award $8,747,908 $8,747,908
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Subawards

Subrecipient Amount Awarded
Institut De Recerca De L'hospital De La Santa Creu I Sant PAU The primary objective of this project period is to conduct the longitudinal follow-up of participants previously enrolled in the HEAD study at baseline. $179,928
Centre De Recherche De L'hopital Douglas Longitudinal multicenter head-to-head harmonization of tau PET tracers $1,151,010
University Of California, San Francisco $126,622
The Regents Of The University Of California Longitudinal Multicenter Head-to-head Harmonization of Tau PET Tracers $1,069,775
Brown University Longitudinal multicenter head-to-head harmonization of tau PET tracers $331,816
Trustees Of Indiana University Longitudinal Multicenter Head-to-head Harmonization of Tau PET Tracers $157,246
Trustees Of Indiana University $65,446
University Of Southern California $100,889
Brown University Longitudinal multicenter head-to-head harmonization of tau PET tracers $331,816
The Royal Institution For The Advancement Of Learning $977,144
The Regents Of The University Of California Longitudinal Multicenter Head-to-head Harmonization of Tau PET Tracers $1,069,775
Centre De Recherche De L'hopital Douglas $561,425
Institut De Recerca De L'hospital De La Santa Creu I Sant PAU Longitudinal multicenter head-to-head harmonization of tau PET tracers $544,320
Brown University Longitudinal Multicenter Head-to-head Harmonization of Tau PET Tracers $507,790
The Methodist Hospital Research Institute $479,978
The Royal Institution For The Advancement Of Learning Longitudinal multicenter head-to-head harmonization of tau PET tracers $2,105,325
Trustees Of Indiana University Longitudinal Multicenter Head-to-head Harmonization of Tau PET Tracers $144,535
Centre De Recherche De L'hopital Douglas $1,047,577
The Methodist Hospital Research Institute $483,854
University Of Southern California $100,889
Centre De Recherche De L'hopital Douglas $555,552
Brown University $219,719
The Regents Of The University Of California $1,069,391
The Washington University $2,827,238
Mayo Clinic $674,221
The Regents Of The University Of California. San Francisco $426,302
Trustees Of Indiana University $157,246
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Quick answers

Who received award R01AG073267?

R01AG073267 was awarded to University Of Pittsburgh - Of The Commonwealth System Of Higher Education by National Institute on Aging (National Institutes of Health) on September 1, 2021.

How much is award R01AG073267 worth?

$92,109,982 has been obligated on R01AG073267: $74,421,072 in federal funding and $17,688,910 in non-federal funding.

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