Alzheimer’s disease (AD), the most common form of dementia, is growing at a rapid pace. It's estimated that there are 44 million people worldwide who suffer from this progressive neurodegenerative disorder that results in memory loss and cognitive decline. In the United States there are 5.5 million people with AD. In fact, someone in the U.S. develops Alzheimer’s disease every 66 seconds, and that number is expected to rise to 16 million people by 2050.1
Although there is currently no cure for Alzheimer’s disease, early prediction is of tremendous importance given that by the time it is clinically diagnosed, neuronal loss has already occurred in many brain and retinal regions.2,3
Current diagnostic tools, such as magnetic resonance imaging (MRI), positron emission tomography (PET) imaging, and cerebrospinal fluid (CSF) biomarkers (Aβ and tau) detection are not only invasive but expensive and carry a high patient burden.3 Furthermore, they add operational challenges. For example, obtaining CSF samples is time-consuming and often difficult in older patients. Most data from PET and CSF come from participants recruited through tertiary care dementia centers.
While PET scans are widely used, they also have potential challenges that may make them a difficult option for providers and patients. These range from high cost, to decreased availability within respective organizations. Additional considerations revolve around the stability of the tracers used in PET scans, i.e., once a PET scan is scheduled, the patient must be available at the correct time and place. This challenge has been particularly noticeable during the COVID-19 pandemic as systemic stress has been placed on the healthcare system.
Importantly, continued assay development now makes it possible to measure ATN biomarkers (amyloid beta [A], pathologic tau [T], and neurodegeneration [N]) in the blood, including the Aβ42/Aβ40 ratio P-tau and NfL. With lower cost and higher accessibility, blood-based AD biomarkers may circumvent the limitations inherent to CSF and imaging.4
Plasma biomarkers provide a promising solution for Alzheimer’s diagnosis
In recent years, scientists have been exploring the use of plasma biomarkers as a non-invasive and cost-effective diagnostic tool for Alzheimer's disease. This option may predict both pathological and clinical changes in those with underlying Alzheimer's, providing a less invasive and less costly way to identify patients who could be candidates for clinical trials or therapies.5
While still in early stages for identifying signs and progression of AD, plasma biomarkers show great promise. P-tau appears to have a high degree of accuracy in plasma for Alzheimer's disease and plasma Aβ measures also have potential. Less invasive and more affordable blood-based biomarker testing along with genetic, clinical and demographic information will likely play an important screening role in selecting individuals for more expensive and invasive biomarker testing.6
Researchers continue to explore different ways to use these markers to improve our understanding of Alzheimer’s progression and develop better treatments. While some biomarkers have been validated, many are still in the infancy stage of development and/or the validation process. However, as more plasma biomarkers complete the validation process, the hypothesis is they will become a standard tool in diagnosis and clinical trial use. As more biomarkers are analyzed, we will have more complete information about the type of dementia a patient has as well as good diagnostic performance, and can predict its progression with greater accuracy, specificity, and sensitivity.7
Currently, plasma biomarkers are being used in clinical trials as an exploratory endpoint. The information obtained from this research has been used to confirm the respective biomarkers being studied are valid for confirming diagnosis of AD.
At IQVIA Biotech, we have the capability within our clinical trial laboratory, Q2 Solutions, to analyze plasma biomarkers. Q2 Solutions has developed several CNS biomarkers including Aβ40/42, Tau/pTau, and Nfl with analysis on high sensitivity immunoassay instruments, such as the Quanterix SiMoA®, to support detection of low levels.
Engaging a CRO early to ensure success
Before any patient is enrolled into a trial, sponsors are strongly encouraged to engage with a CRO partner with specific CNS experience to construct a comprehensive clinical development strategy, thus leading to alignment in strategic direction and improving the probability of success.
By integrating a partner early in the process, issues that can arise during preclinical and clinical development can be avoided. A CRO can lead discussions while keeping feasibility, risks, costs and timelines in mind. There are real opportunities to enhance study delivery through predictive or machine-learning approaches and provide direct insight into patient populations and sites that can aid in performance and timelines.
Supporting CNS clinical trials at every step
With the multitude of challenges facing CNS clinical trials, having a partner that understands neuroradiology, biomarker development, clinical trial design, and novel delivery scenarios is key to helping optimize your CNS program. We have a proven track record of helping sponsors develop the right protocol, select the correct population, and identify the right site and country mix to perform your clinical study. Leveraging our scientific experts, data and global resources enables you to focus on what matter most: getting breakthrough treatments to patients in need.
Contact us to discuss how we can help support your CNS clinical trial.
References
1. https://alzheimersnewstoday.com/alzheimers-disease-statistics/
2. https://journals.sagepub.com/doi/10.1177/1533317519848239
3. https://www.mdpi.com/2075-4426/10/3/114/htm
4. https://www.nature.com/articles/s41467-021-23746-0
5. https://www.jwatch.org/na53724/2021/06/23/are-plasma-biomarkers-useful-those-without-dementia/
6. https://www.sciencedirect.com/science/article/pii/S1552526018300724
7. https://pubmed.ncbi.nlm.nih.gov/31072117/