Alzheimer's disease: early detection using an eye exam

Alzheimer's disease is still incurable, but if detected early enough, countermeasures can improve treatment and slow the progression. Unfortunately, there is still no reliable early detection test at this juncture. This might soon change thanks to a non-invasive spectroscopy of the retina.

In this MEDICA-tradefair.com interview, Dr. Izabella Jahn and Dr. Clara Stiebing explain how Raman spectroscopy works, describe its advantages over other optical imaging methods, and reveal how it could facilitate the early detection of Alzheimer's disease.

Dr. Jahn, Dr. Stiebing, how does Raman spectroscopy work?

Dr. Izabella Jahn: Raman spectroscopy is based on vibrational excitation of molecules. The result is an inelastic scattering of light, meaning there is an exchange of energy between light and matter. A laser in the visible to near infrared range is used as an excitation source. Each molecular bond exhibits a unique characteristic vibration and thus its own Raman band. A Raman spectrum is recorded, which contains comprehensive molecular information about a sample. Raman spectra are hence also referred to as "molecular fingerprints".

Dr. Clara Stiebing: Raman spectroscopy enables us to decipher the biochemical composition of samples. With tissue samples, the technique provides detailed information about present lipids, proteins, nucleic acids, pigments, and collagens.

You use Raman spectroscopy to examine retinal tissue. What information do you get from this method?  

Stiebing: We primarily obtain information about proteins, but we can also detect rhodopsin, the biological pigment found in the rods of the retina. In an earlier publication, we showed we can also identify the fovea in ex vivo human retina. This is the area of best vision, the so-called yellow spot, which has a high concentration of carotenoids.

In the MOON project, you teamed up with the Medical University of Vienna to study whether biochemical changes in the retina might indicate the early stages of Alzheimer's disease. How do you discriminate between healthy and diseased tissue?

Jahn: The differences in the spectral range are very minor and nearly unrecognizable to the naked eye. That is why we use chemometric algorithms to detect the differences. These algorithms are designed to classify the samples in a mathematical model.

Stiebing: Simply put, the statement in a model might be: "The increased expression of a specific protein in a setting indicates healthy or diseased tissue.” The tissue would then be classified based on the algorithms.

What is the advantage over other analytical methods?

Stiebing: Unlike fluorescence spectroscopy, for example, Raman spectroscopy does not need dyes to achieve coloration. We can also bypass the typical histological staining of ex vivo slices and have been able to demonstrate that we can identify the individual layers of the retina based on cross sections. This makes Raman spectroscopy a method that can also be used for in vivo diagnosis.

Compared to other retinal examination methods, Raman spectroscopy also provides additional, detailed biochemical information, while standard tests such as optical coherence tomography (OCT) primarily diagnose morphological changes. Raman spectroscopy thus gives physicians information that was not previously available.

Where does the idea of examining the retina come from?

Jahn: Scientific literature suggests that there are biochemical changes in the early stages of retinal disease that do not lead to any structural change. Raman spectroscopy provides information on the biochemical composition of biological tissues, making it a method that could visualize these changes. Like the brain, the retina is made up of nervous tissue. The optic nerve is a group of nerve fibers that connect the eye to the brain. Hence, the hypothesis is that progressive neurodegenerative diseases such as Alzheimer's disease also manifest in the retina. There is increasing evidence of this in scientific literature.

That is why the idea behind the MOON project was to combine the advantages of standard optical coherence tomography (OCT) with Raman spectroscopy to create a comprehensive, detailed view of the retina.

A device that combines Raman spectroscopy with OCT is currently in development. What is your role in this process?

Stiebing: Our project partners at the Medical University of Vienna have applied for device approval, which should be accepted soon. The device can subsequently be tested in vivo on the first patients. We continue to collaborate closely together and leverage our expertise in Raman spectroscopy analysis in hopes that this will also shed light on the diagnostic benefits.