Longitudinal validation of retinal biomarkers against cerebral imaging in preclinical alzheimer's disease
Active Project Grant Awarded Last action
- Award ID
- R01AG079241
- Recipient
-
University Of Rhode Island UEI CJDNG9D14MW7 Part of State Of Rhode Island
- Awarding agency
-
National Institute on Aging
National Institutes of Health, Department of Health and Human Services
- Obligated
- $23,278,933
Award facts
- Assistance listing
- 93.866 Aging Research
- Completion date 88% complete
- Place of performance
- Kingston, RI 02881, USA
Award details come from USAspending.gov.
Description
- Abstract
- Alzheimer's disease (ad) is a gradually progressive neurodegenerative disorder that results in total cognitive and functional loss. To date, disease-modifying therapeutics and secondary prevention efforts have proven ineffective in combating this public health burden, which impacts over 5.8 million individuals, and is the 6TH leading cause of death in the united states. The proposed study addresses the critical need for minimally invasive, cost-efficient, scalable, and accessible ad risk screening biomarkers capable of detecting ad in the earliest pathologic stages (preclinical ad) before clinical symptoms are evident. We target biomarkers in the human retina, a part of the central nervous system (CNS), as they can be visualized non-invasively using standard ophthalmologic techniques and show promise for early ad risk detection and disease monitoring. The atlas of retinal imaging in alzheimer's study (ARIAS) is a longitudinal, observational cohort study to identify sensitive and specific retinal biomarkers of preclinical ad and define their context of use. The objective of the proposed project is to leverage the existing ARIAS infrastructure, adding reference standard brain imaging biomarkers (3T MRI, AB pet) and novel plasma biomarkers (PTAU231, PTAU181) to test the central hypothesis that retinal biomarker alterations will predict cerebral biomarker changes and mirror longitudinal cerebral biomarker changes in preclinical ad. Four specific aims will be pursued: (1) identify retinal biomarker differences between preclinical ad participants and cognitively unimpaired (CU) older adults; (2) validate candidate retinal biomarkers cross-sectionally against cerebral biomarkers using AB pet as a measure of cerebral amyloidosis and MRI as a measure of neurodegeneration; (3) determine the longitudinal relationship between retinal and brain imaging biomarkers, and the ability of baseline retinal biomarkers to predict cognitive and/or brain imaging biomarker changes over 3-year follow-up; and (4) (EXPLORATORY) assess the combined sensitivity and specificity of candidate retinal biomarkers with emergent plasma biomarkers in ad risk prediction. Work will be carried out at one existing ARIAS site and two high performing ad research sites. CU participants will complete 5 study visits: screening, baseline, year (Y) 1, Y2, and Y3 follow-up. Brain imaging (MRI and AB pet) and plasma analysis will occur at baseline and Y3 follow-up. Retinal imaging and cognitive evaluation will occur at baseline and Y1, Y2, and Y3 follow-up. Brain imaging, retinal imaging, cognitive evaluation, and plasma analysis will be supported by four respective cores. Validating retinal biomarkers in preclinical ad is expected to shift focus in ad retinal biomarker development towards systemic, quantitative characterization of retinal risk biomarkers scalable for population-based ad risk screening. Combining plasma biomarkers with sensitive and specific retinal biomarkers could transform ad risk assessment, allowing identification of ad-related changes decades before clinical onset, which may offer the best chance of therapeutic success. Clinical applications include population-based screening for ideal candidates for emerging secondary prevention therapeutics.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $2,002,901 | |
| Amendment | $0 | |
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| Amendment | $1,984,309 | |
| Amendment | $1,984,309 | |
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| Amendment | $0 | |
| Amendment | $1,786,110 | |
| Amendment | $1,786,110 | |
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| Amendment | $0 | |
| Amendment | $2,012,035 | |
| Amendment | $2,012,035 | |
| Amendment | $2,012,035 | |
| Amendment | $0 | |
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| Amendment | $0 | |
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| Amendment | $0 | |
| Amendment | $2,566,363 | |
| Amendment | $2,566,363 | |
| Original award | $2,566,363 |
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Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| The University Of North Texas Health Science Center At Fort Worth | $360,583 | |
| Butler Hospital | $463,025 | |
| The University Of North Texas Health Science Center At Fort Worth | $125,431 | |
| The University Of North Texas Health Science Center At Fort Worth | $165,238 | |
| Brown University | $597,783 | |
| The Washington University | $191,433 | |
| Brown University | $481,783 | |
| The Washington University | $1,936,467 | |
| Butler Hospital | $284,243 | |
| Brown University | $233,083 | |
| The Washington University | $898,780 | |
| Butler Hospital | $463,025 | |
| The Washington University | $699,542 | |
| The Washington University | $458,894 | |
| The Washington University | $316,254 | |
| The Washington University | $1,104,217 | |
| Brown University | $1,009,536 |
Show all 17
Quick answers
Who received award R01AG079241?
R01AG079241 was awarded to University Of Rhode Island by National Institute on Aging (National Institutes of Health) on September 15, 2022.
How much is award R01AG079241 worth?
$23,278,933 has been obligated on R01AG079241.
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