image: OHSU scientist Lei Wang, Ph.D., is part of a new federally funded initiative to develop an eye scan to detect early screening for Alzheimer’s disease. Wang, an organic chemist by training, is collaborating with OHSU imaging expert Yifan Jian, Ph.D. If the research initiative succeeds, it could result in a low-cost and widely accessible screening tool.
Credit: OHSU/Erik Robinson
The human eye may literally become a window revealing the earliest signals of Alzheimer’s disease, thanks to a new federally funded research initiative at Oregon Health & Science University.
The new five-year, $3.3 million award will enable OHSU scientists to develop an eye drop specially designed to detect the fluorescent signal of a protein associated with Alzheimer’s. Combined with the use of a noninvasive scanner, the research project could result in a low-cost, widely accessible screening tool to catch the earliest stage of the disease.
“We’re looking for early-stage patients who don’t have symptoms,” said project leader Lei Wang, Ph.D., assistant professor of biomedical engineering in the OHSU School of Medicine. Wang is also part of the OHSU Knight Cancer Institute and leads the Molecular Imaging and Probe Development Laboratory. “The goal is to develop population-level screening involving a simple eye drop and a quick scan.”
The project is considered high-risk, high-reward.
If it works, it could greatly improve outcomes in new treatments for Alzheimer’s that are most beneficial in the earliest stages of the disease’s progression.
The project is funded through a program of the National Institute on Aging of the National Institutes of Health designed for early-stage investigators. Named for the late NIH scientist Stephen I. Katz, the award encourages scientists early in their career to develop new approaches to solving biomedical problems.
Wang’s initiative would add to promising results using blood-based biomarkers to detect Alzheimer’s.
Wang said the OHSU initiative, if successful, wouldn’t necessarily require patients to travel to a specialized center. He envisions the technique would ultimately be available in ophthalmology clinics in rural and urban areas alike, scaling up the ability to quickly and efficiently screen people for early signals of Alzheimer’s.
“It would be low-cost and accessible, not limited to major cities like Portland or Seattle,” he said.
That’s especially important because even though new treatments have demonstrated effectiveness in slowing the progression of Alzheimer’s, they are most effective in the earlier stages of the disease.
Retina: Neural sensory extension of the brain
Trained as an organic chemist, Wang has extensive experience in developing fluorescent contrasting agents useful in helping surgeons to remove tumors while preserving critical structures such as nerve tissue. His lab focuses on designing small-molecule fluorophores — which absorb and emit light — and quantitative imaging technologies that can be translated into real-world clinical tools.
In the case of Alzheimer’s disease, Wang’s focus is on a type of protein called amyloid.
Typically, scientists associate Alzheimer’s with amyloid-beta and tau proteins clumping together in the brain, which is believed to be involved in neurodegeneration leading to symptoms of cognitive decline that characterizes the disease. New antibody treatments attempt to slow cognitive decline by targeting amyloid plaques in the brain.
It’s possible to detect amyloid plaques through brain imaging, but those tests are expensive and not typically used in screening in otherwise healthy patients.
Instead, Wang is proposing to glimpse amyloid proteins by developing a fluorescence-based molecule that ultimately could be applied as an eye drop.
He is collaborating with retinal imaging expert Yifan Jian, Ph.D., associate professor ophthalmology and biomedical engineering in the OHSU School of Medicine, to use an ultrawide field fluorescence scanning laser ophthalmoscope to detect amyloid revealed through the retina.
Jian will focus on refining the imaging technology.
“Working with Lei, we’re planning to tailor wave lengths that are safe for the retina while providing the contrast we need for the amyloid proteins to stand out,” Jian said. “This is a collaborative effort, and we think we have a strong foundation to start the work.”
The retina shares a direct connection to the brain and is the only part of the central nervous system that can be imaged noninvasively at cellular resolution.
“The retina is a neural sensory extension of the brain,” Wang said. “If we can detect a buildup of amyloid in the retina, it may be possible to flag early-stage Alzheimer’s among patients who aren’t yet experiencing any symptoms. That’s the foundation of this project.”
People flagged through retinal screening could then be referred to a neurologist for diagnosis and more intensive brain imaging.
Wang will work with a multidisciplinary team of co-investigators to advance the project from concept toward the clinic.
Jian will contribute expertise in retinal imaging and ultrawide field fluorescence scanning laser ophthalmoscopy. Nora Gray, Ph.D., associate professor of neurology in the OHSU School of Medicine, will contribute expertise in Alzheimer’s disease models and retinal pathology. Summer Gibbs, Ph.D., professor of biomedical engineering, brings extensive experience in the clinical translation of fluorescent contrast agents and first-in-human imaging studies. Randy Woltjer, M.D., Ph.D., professor of pathology and laboratory medicine and director of the Neuropathology Core in OHSU’s Layton Aging & Alzheimer’s Disease Center, will help guide clinical priorities and future translation to patient care.
The five-year research project will involve developing the fluorescent contrasting agent and then testing it for safety and efficacy in a mouse model. Only then would it advance beyond the lab to a clinical trial.
“We’re always thinking about how this can be useful for patients,” Wang said. “The long-term vision is something that is accurate, affordable, and available in many communities, not only at large academic centers.”