Put Your Finger on It

by Women’s Brain Health Initiative:

CELLULAR FINGERPRINTING FOR EARLY ALZHEIMER’S DIAGNOSIS.

Dementia is not only one of the most pressing global health challenges, but it is also a condition that lacks both effective treatments and a reliable means of early diagnosis. According to the Alzheimer Society of Canada, more than half a million Canadians are suffering from dementia, and that number is expected to exceed 900,000 by 2030. Currently, the most common form of dementia, Alzheimer’s disease, can only be definitively diagnosed after death through examination of brain tissue.

“People with dementia are impatient, they have lived for too long with very few therapeutic or diagnostic breakthroughs,” said Dr. Saskia Sivananthan, Chief Research and Knowledge, Translation and Exchange Officer with the Alzheimer Society of Canada.

Thankfully, however, there is hope on the horizon.

USING INFRARED LIGHT FOR EARLY DETECTION

Researchers around the world are exploring a variety of approaches for early diagnosis. One of the most promising methods comes from a research team at the University of California’s Lawrence Berkeley National Laboratory (Berkeley Lab) who are investigating the use of skin cell analysis as a means of detecting disorders elsewhere in the body, including the brain.

THE TECHNIQUE, KNOWN AS “SPECTRAL PHENOTYPING,” INVOLVES EXPOSING SKIN CELLS TO INFRARED LIGHT, WHICH CAUSES THE MOLECULES WITHIN THE CELLS TO VIBRATE.

Project leader Dr. Cynthia McMurray told Mind Over Matter® that her team has discovered a way to analyze the vibrations and identify unique differences between healthy individuals and those with Alzheimer’s disease.

“Many scientists focus on specific biological molecules as biomarkers for disease, but here’s a technique that uses light to create vibrational chemistry that can then be computationally analyzed for a very specific disease biomarker,” explained Dr. McMurray, Senior Scientist at the Berkeley Lab.

She noted that the differences are so distinctive that she likens the process to “cellular fingerprinting.”

Scientists already knew that cells would react when exposed to infrared light. The challenge for Dr. McMurray’s team was figuring out how to analyze the vibrations. The answer came with the development of a computer algorithm that could identify the differences – an aspect of the project led by her colleague
Dr. Ben Brown.

The researchers first tried the technique on the brain cells of mice, comparing healthy tissue with those with Huntington’s disease. “It was beautiful. The first time we tested the mature method on cells, it worked,” said Dr. McMurray.

The research team then successfully transitioned to human subjects, adjusting their algorithm and using skin cells from an existing tissue bank to compare healthy individuals with those with Alzheimer’s disease.

We were able to see very clearly the differences. It was quick, definitive, and exciting.

Dr. McMurray continued: “It was a huge step forward because now we can follow the disease without accessing the brain or using complicated procedures, so it was a big breakthrough for us.”

Her team’s successful proof-of-principle study was published in Scientific Reports in August 2021.

NEXT STEPS

While Dr. McMurray is confident that spectral phenotyping is an effective diagnostic tool, there is still important work ahead. Her team is currently conducting studies with a larger group of participants with Alzheimer’s disease. Dr. McMurray wants to ensure that the procedure delivers an accurate diagnosis, and that it does not mistake other neurodegenerative diseases for Alzheimer’s disease.

DEVELOPING A RELIABLE MEANS OF EARLY DIAGNOSIS FOR ALZHEIMER’S DISEASE COULD HAVE A PROFOUND IMPACT.

It is well-established that changes in the brain begin many years (and even decades) before symptoms emerge. Early diagnosis could mean earlier interventions, adjustments in lifestyle that can slow the onset of the disease, and more advance planning. As treatments are developed, they can be administered before symptoms start to show.

Dr. Sivananthan of the Alzheimer Society of Canada noted that while there has been progress in identifying biomarkers that can indicate the early stages of the disease, many are not yet available for day-to-day clinical use.

“Those that are available, such as computerized tomography (CT) or magnetic resonance imaging (MRI), require expensive equipment and can involve painful, invasive methods such as collecting spinal fluid,” she said. “These tests are only available once symptoms of Alzheimer’s or other forms of dementia are present.”

Dr. Sivananthan cites blood-based biomarkers, more sophisticated imaging, and eye tracking as diagnostic methods that are showing real promise. The Alzheimer Society Research Program, which funds new and innovative research into the causes of dementia, has specifically supported this type of proof-of-concept research.

“There are several promising developments for early diagnosis of Alzheimer’s disease that I am hopeful will come to market in the next five to ten years, likely in combination with an existing method,” she said.

When asked about the Berkeley Lab’s spectral phenotyping project, Dr. Sivananthan noted that “any research that can accurately and reliably diagnose dementia early, without invasive methods, is a key step forward for the field.”

Dr. McMurray is interested in exploring whether the procedure could also work using cheek swabs – a simple and painless means of collective cell samples. Her vision is to make spectral phenotyping widely available as an effective, non-invasive, and inexpensive diagnostic tool, one that she believes has the potential to detect a wide variety of diseases beyond dementia, including cancer.