# Validation of Retinal Abeta as a Potential Biomarker of Alzheimer's Disease

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $721,824

## Abstract

PROJECT SUMMARY
This application addresses the overarching challenge of detection of the early onset of β-amyloid plaques
(Abeta) in Alzheimer's disease (AD). It does so by proposing a novel approach to image retinal Abeta by using
signals emitted by curcumin fluorescence (FL). AD is the most common cause of dementia among elderly
people. Its pathology is characterized by the presence of extracellular deposits of misfolded and aggregated
Abeta peptides, which subsequently spread from the hippocampus to the cerebral cortex causing neuronal
death and ultimately loss of memory, logic and the ability to speak. At present, no disease-modifying therapy is
effective against AD nor it is possible to diagnose the early onset and/or the progress of the disease.
 Recent findings indicate that elevated levels of Abeta proteins are associated with dysfunctional
neuronal networks both in the brain and eyes. Because AD undergoes a protracted asymptomatic stage before
it reaches the advanced stage, a window of opportunity exists for early intervention, and successful detection
of the early onset of the disease via routine screening will improve therapeutic outcomes and save lives. In that
regard, early detection of Abeta in the eyes at ophthalmology centers, widely available in every health
community settings seems ideal in terms of practicality, feasibility, safety and cost.
 Recently, our group demonstrated a novel approach for delivery of curcumin in vivo via inhalation of the
curcumin aerosol. Further, in collaboration with Professor Joanne Matsubara, we recently demonstrated that
inhaling curcumin aerosol resulted in significant accumulation of the compound in the retina. Further, we also
demonstrated that curcumin binds to Abeta in retinal sublayers. Building on that foundation, we hypothesize
that curcumin FL in the eyes can be used as a surrogate biomarker for assessing Abeta levels in the brain. Our
long-term objective is to (i) demonstrate the newly synthesized curcumin analogs can be distributed and bind
effectively to retinal Abeta; (ii) demonstrate retinal Abeta as a early biomarker of AD.
 A less well developed, but potentially powerful approach, marrying medicinal chemistry with drug
delivery, and targeted molecular imaging, for high sensitivity molecular “fingerprinting” of AD in vivo, is the
subject of this high risk-high reward proposal.

## Key facts

- **NIH application ID:** 9999388
- **Project number:** 5R01AG061138-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Wellington Pham
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $721,824
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999388

## Citation

> US National Institutes of Health, RePORTER application 9999388, Validation of Retinal Abeta as a Potential Biomarker of Alzheimer's Disease (5R01AG061138-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999388. Licensed CC0.

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