Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.
If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.
This week’s study is…
Amyloid-beta misfolding and GFAP predict risk of clinical Alzheimer’s disease diagnosis within 17 years
We previously published about this research in a story titled “A Biomarker That Detects Alzheimer’s Disease (AD) Seventeen Years Before Outward Symptoms Appear” which can be found here. The study was originally published in the scientific journal Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. You can read the full text of the study here.
This research team was affiliated with the Centre for Protein Diagnostics at Ruhr-Universität Bochum and the German Cancer Research Centre in Heidelberg.
What Happened?
Alzheimer’s disease has very limited therapeutic options that ultimately fail to have a major effect on the disease course. Prior research has indicated that the mechanism of action in this disease can begin up to 20 years before symptoms and signs begin to appear. In this study, a team of researchers sought to determine if there was a method that could detect signs of Alzheimer’s years or even decades before symptoms begin. If so, then it might be possible for treatment to begin much earlier, when it would potentially be much more effective.
The research involved the analysis of blood plasma in study participants, who were between age 50 and 75 and had not yet been diagnosed with Alzheimer’s disease. These samples were taken at the beginning of the study and were frozen. The study compared 68 people that had been diagnosed during the 17 year follow up period to a control group of 240 people that didn’t have the disease. The research also centered around the use of an innovative device to detect early signs of the illness: an immuno-infrared sensor.
The sensor was able to correctly identify the 68 people that ultimately developed the disease. The scientists used highly sensitive SIMOA as a comparison to evaluated other biomarkers, most specifically P-tau181. The team found, however, that this biomarker was not suitable for detecting Alzheimer’s in the pre-clinical stage. Instead, the researchers found that SIMOA was able to use levels of glial fiber protein (GFAP) to predict the disease up to 17 years in advance. However, it’s accuracy was less precise than the immuno-infrared sensor. However, the team was able to improve accuracy when combining this marker with the detection of amyloid-beta protein misfolding.
Overall, misfolding amyloid-beta and GFAP were the best biomarkers for predicting Alzheimer’s in the preclinical stage using either SIMOA or the immuno-infrared sensor.
About Alzheimer’s Disease
Alzheimer’s disease, often just called Alzheimer’s, is a neurodegenerative illness affecting the brain that is primarily characterized by memory loss and dementia, which progressively worsens over time. Alzheimer’s disease is the leading cause of dementia around the world, being linked to around 70 percent of cases. The cause of this disease isn’t clear, but a family history of the disease, particularly in the patient’s parents, appears to be the dominant risk factor. Other possible factors may include high blood pressure, depression, and head injuries. Memory decline is often the first recognized symptom; others include mood swings, disorientation, and difficulty speaking; these symptoms worsen over time to the extent that the person cannot function in daily life; paranoia, aggression, and then apathy are common. Treatment is symptomatic and supportive, and no known medications can halt disease progression. Life expectancy following diagnosis is between three to nine years. To learn more about Alzheimer’s disease, click here.
Why Does it Matter?
Earlier detection of Alzheimer’s disease can give physicians and researchers a critical step ahead of the worst manifestations of the illness. The scientists hope is that if the disease can be detected early enough in high-risk individuals, then treatment can begin years or even decades in advance of symptoms. This could magnify the effectiveness of current treatments such as Aduhelm, which has minimal effectiveness in patients experiencing symptoms.
“The exact timing of therapeutic intervention will become even more important in the future. The success of future drug trials will depend on the study participants being correctly characterized and not yet showing irreversible damage at study entry.” – Léon Breyer, Ph.D, first author
Future goals include bringing the immuno-infrared sensor to market maturity, since it can detect the disease more reliably and much earlier than current methods. The majority of Alzheimer’s clinical trials have failed, and this may be primarily because the patients in the trial have already suffered damage that cannot be reversed:
“It seems that once plaques are deposited, they induce irreversible damage in the brain.” – Klaus Gerwert, professor, director of the Centre for Protein Diagnostics
The results of this study may be crucial to improving outcomes in Alzheimer’s disease in the future.
