# Retinal Light Scattering Measurements as a Clinical Biomarker of Alzheimer's Disease

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $491,598

## Abstract

Project Summary
The overall objective of this proposal is to demonstrate the clinical feasibility of a novel method
Although deposition of amyloid plaques in brain tissue is the clearest pathological
indicator of AD, it can only be detected during autopsy or positron emission tomography (PET)
imaging, which can be prohibitively expensive. As a result, the most widely used approach for
diagnosing AD continues to be the clinical recognition of cognitive impairment, a subjective
evaluation which only provides probable diagnosis when other causes of dementia are eliminated.
Because the optic nerve and retina are extensions of the central nervous system, several
investigations to seek have sought to link retinal features with onset of the disease. Using optical
coherence tomography (OCT), a correlation has been observed between thinning of the retinal
nerve fiber layer and AD but this feature can also indicate other diseases. Instead, we propose
to develop a diagnostic based on measuring structural features in the various layers of the retina,
specifically to identify a diagnostic metric of AD that is potentially distinct from other pathologies.
To meet this objective, we seek to develop angle-resolved low coherence interferometry (a/LCI)
for clinical measurement of structural features of retinal layers. a/LCI is a light scattering method
that combines the sub-cellular sensitivity of light scattering with the depth resolution of OCT. It
has been shown to detect precancerous cells in esophagus and cervix using in vivo depth
resolved measurements of nuclear morphology. Rather than imaging the cellular structure of the
retina directly, we instead propose to use a/LCI to measure the micron-scale structural
characteristics of retinal layers. Preliminary data shows that a/LCI measurements of the
organization of these structures correlates with presence of AD in a murine model. The following
Specific Aims are proposed: 1. Implement integrated a/LCI & OCT system for in vivo studies of
the human retina. 2. Characterize retinal features in AD patients with a/LCI & OCT. This study
will confirm measurements from the animal model and provide data for establishing biomarkers
of AD in humans. 3. Conduct data analysis for biomarker development using morphological
descriptors and machine learning. 4. Perform in vivo prospective studies in AD patients to validate
biomarkers of structural changes as predictive of disease. Upon completion of this project, we will
have shown feasibility and provided justification for future development of a combined a/LCI &
OCT system for clinical screening for AD.

## Key facts

- **NIH application ID:** 10788366
- **Project number:** 5R01AG072732-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Adam Wax
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $491,598
- **Award type:** 5
- **Project period:** 2022-06-15 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10788366

## Citation

> US National Institutes of Health, RePORTER application 10788366, Retinal Light Scattering Measurements as a Clinical Biomarker of Alzheimer's Disease (5R01AG072732-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10788366. Licensed CC0.

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