# Retinal Imaging of Alzheimer's Disease Pathology

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2020 · $437,500

## Abstract

ABSTRACT
The central goal of this proposal is to explore pathological hallmarks of Alzheimer’s disease (AD) in the retina
and evaluate retinal amyloid imaging as a novel approach for diagnosis and monitoring of AD. There is growing
evidence that AD affects the neurosensory retina, a developmental outgrowth of the brain and the only CNS
tissue directly accessible for high-resolution imaging. The retina exhibits a wide spectrum of pathologies in AD
patients, including thinning of the nerve fiber layer, vascular and blood flow changes, and degeneration of retinal
ganglion cells (RGCs). The hallmark pathological signs of AD – amyloid β-protein (Aβ) plaques and neurofibrillary
tangles (NFT) comprised of hyperphosphorylated tau protein (ptau) – have long been described in the brain.
However, Aβ deposits in the retina of human AD patients, including early stage cases, were only recently
discovered. Further studies have found ptau, Aβ-like deposits, and elevated Aβ42 peptides in postmortem AD
retinas. Notably, a loss of a subtype of RGCs, melanopsin-containing RGCs, was associated with accumulation
of Aβ inside and around these cells. Preliminary data from our group indicate manifestation of vascular
amyloidosis and retinal inflammation (e.g. astrogliosis and microgliosis) surrounding Aβ fibrils and NFT-like
structures, which are specific to the retinas of AD patients. These changes appear to be exacerbated during
disease progression. In order to visualize AD pathology, a noninvasive retinal amyloid imaging method has been
developed to facilitate repeated monitoring of retinal Aβ deposits with high resolution and specificity in living
transgenic rodent models of AD. Pilot clinical trials implementing this retinal curcumin imaging technology
demonstrate its capacity to quantitatively detect retinal Aβ deposits in living AD patients. Our studies using this
retinal amyloid optical imaging in mouse models demonstrate the feasibility to track subtle changes in retinal
amyloid plaques during disease progression, and in response to immune-based therapy. Based on the published
and preliminary data collected, the following research objectives are proposed: 1) To determine the existence
and distribution of amyloid deposits, vascular amyloidosis, intracellular Aβ oligomers, and tauopathy in the retinas
of AD and Mild Cognitive Impairment (MCI) patients; 2) To examine retinal inflammation and degeneration, and
evaluate possible correlations with brain pathology and cognitive status in MCI and AD patients, and 3) To
noninvasively monitor formation, appearance and clearance of retinal Aβ deposits in live mouse models of AD,
during disease progression and in response to immunotherapy. Results from these studies stand to markedly
increase the understanding of how AD affects the retina, and whether retinal amyloid imaging can reliably indicate
brain pathology or cognitive status. Given the accessibility of the retina for direct and noninvasive high resolution
imaging, ta...

## Key facts

- **NIH application ID:** 9932262
- **Project number:** 5R01AG056478-04
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Maya Koronyo-Hamaoui
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $437,500
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932262

## Citation

> US National Institutes of Health, RePORTER application 9932262, Retinal Imaging of Alzheimer's Disease Pathology (5R01AG056478-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9932262. Licensed CC0.

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