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ARCAM-1 Facilitates Fluorescence Detection of Amyloid-Containing Deposits in the Retina
Kevin J Cao1, John H Kim1, Heike Kroeger2,3
1Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
Purpose:
To investigate the use of an amyloid-targeting fluorescent probe, ARCAM-1, to identify amyloid-containing deposits in the retina of a transgenic mouse model of Alzheimer's disease (AD) and in human postmortem AD patients.
Methods:
Aged APP/PS1 transgenic AD and wild-type (WT) mice were given an intraperitoneal (IP) injection of ARCAM-1 and their retinas imaged in vivo using a fluorescence ophthalmoscope. Eyes were enucleated and dissected for ex vivo inspection of retinal amyloid deposits. Additionally, formalin-fixed eyes from human AD and control patients were dissected, and the retinas were stained using ARCAM-1 or with an anti-amyloid-β antibody. Confocal microscopy was used to image amyloid-containing deposits stained with ARCAM-1 or with immunostaining.
Results:
Four out of eight APP/PS1 mice showed the presence of amyloid aggregates in the retina during antemortem imaging. Retinas from three human AD patients stained with ARCAM-1 showed an apparent increased density of fluorescently labeled amyloid-containing deposits compared to the retinas from two healthy, cognitively normal (CN) patients. Immunolabeling confirmed the presence of amyloid deposits in both the retinal neuronal layers and in retinal vasculature.
Conclusions:
ARCAM-1 facilitates antemortem detection of amyloid aggregates in the retina of a mouse model for AD, and postmortem detection of amyloid-containing deposits in human retinal tissues from AD patients. These results support the hypothesis of AD pathology manifesting in the eye and highlight a novel area for fluorophore development for the optical detection of retinal amyloid in AD patients.
Translational Relevance:
This paper represents an initial examination for potential translation of an amyloid-targeting fluorescent probe to a retinal imaging agent for aiding in the diagnosis of Alzheimer's disease.
Insights
This study shows the fluorescent probe ARCAM-1 can detect amyloid deposits in the retinas of Alzheimer's disease (AD) mouse models and human patients, suggesting eye pathology in AD.
Area of Science:
- Ophthalmology
- Neurology
- Biomedical Imaging
Background:
- Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) plaque accumulation.
- The retina may be a site for AD pathology, offering potential for early diagnosis.
- Current diagnostic methods for AD are invasive or lack sensitivity for early-stage detection.
Purpose of the Study:
- To evaluate the efficacy of ARCAM-1, an amyloid-targeting fluorescent probe, for identifying retinal amyloid deposits.
- To assess ARCAM-1's utility in both a transgenic mouse model of AD and postmortem human AD retinas.
Main Methods:
- ARCAM-1 was administered to aged APP/PS1 transgenic AD mice and wild-type (WT) controls.
- Retinal imaging was performed in vivo using fluorescence ophthalmoscopy and ex vivo via confocal microscopy.
- Human postmortem retinas from AD patients and healthy controls were stained with ARCAM-1 and anti-Aβ antibody for comparison.
Main Results:
- Amyloid aggregates were detected in the retinas of 4/8 APP/PS1 mice via antemortem imaging.
- ARCAM-1 staining revealed increased fluorescent deposits in human AD retinas compared to controls.
- Immunolabeling confirmed amyloid presence in retinal neuronal layers and vasculature.
Conclusions:
- ARCAM-1 enables antemortem detection of retinal amyloid in an AD mouse model.
- The probe facilitates postmortem identification of amyloid deposits in human AD retinas.
- These findings support ocular manifestations of AD and suggest ARCAM-1 as a potential diagnostic imaging agent.
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