# Alzheimer's Disease Hallmark Pathology and Associated Inflammation in the Retina

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2021 · $306,690

## Abstract

ABSTRACT
The central goal of this proposal is to explore pathological hallmarks of Alzheimer’s disease (AD) and
associated inflammation in retinas from post-mortem humans and in live mouse models. These studies will
provide the basic pathological information to permit development of second-generation retinal imaging
methods to diagnose, assess progression, and monitor treatments for AD. The hallmark pathological signs of
AD in the brain – amyloid β-protein (Aβ) plaques and neurofibrillary tangles (NFTs) comprised of
hyperphosphorylated tau protein – are also present in the retina. The retina exhibits a wide spectrum of
pathologies in AD patients, including thinning of the nerve fiber layer, vascular changes, and degeneration of
retinal ganglion cells. However, only recently were AD-specific hallmark Aβ deposits identified by our group in
retinas of AD patients and early-stage cases. Further, our preliminary data indicate manifestation of vascular
amyloid deposits and retinal inflammation (e.g. astrogliosis, microgliosis) surrounding Aβ aggregation and
NFT-like structures, which are specific to the retinas of AD patients. To visualize amyloid pathology, we
developed a noninvasive retinal curcumin imaging approach for repeated monitoring of retinal Aβ deposits with
high resolution and specificity in living transgenic mouse models of AD. Preliminary studies also demonstrate
the feasibility of using an optical imaging device to track infiltration of fluorescently labeled immune cells into
the live mouse retina. Data from ongoing clinical trials implementing this retinal curcumin imaging technology
demonstrate its capacity to quantitatively detect retinal Aβ deposits in living AD patients, but establishing
specificity for AD and the ability to faithfully predict cerebral pathology during disease progression presents a
significant challenge. In this study, paired samples of retina and brain from subjects with AD with or without
cerebral amyloid angiopathy and from controls including mild cognitive impairment will be assessed for the
spatial distribution of AD-related and inflammatory markers; retinal findings will be correlated with those in the
corresponding brain. The following research objectives are proposed: 1) to determine the existence and
distribution of abluminal and vascular Aβ deposits, intracellular Aβ oligomers, and tauopathy during disease
progression in the retina of AD and MCI patients, and to compare retinal pathology to that in the paired brain
sample; 2) to investigate the Aβ-associated local inflammation, infiltrating monocytes and their involvement in
Aβ uptake, and co-occurrence of astrogliosis and glial cell death in retinas of AD and MCI patients; and 3) to
noninvasively monitor formation and clearance of retinal Aβ deposits and monocytes infiltration during disease
progression and in response to immune-based therapy in live mouse models of AD. Results from these studies
stand to markedly increase the understanding of how AD aff...

## Key facts

- **NIH application ID:** 10087458
- **Project number:** 5R01AG055865-04
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Maya Koronyo-Hamaoui
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $306,690
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10087458

## Citation

> US National Institutes of Health, RePORTER application 10087458, Alzheimer's Disease Hallmark Pathology and Associated Inflammation in the Retina (5R01AG055865-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10087458. Licensed CC0.

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