Biomarkers have revolutionized the understanding of Alzheimer’s disease (AD), enabling early detection and opening the door to personalized treatments. A series of six papers published in The Lancet Healthy Longevity and eBioMedicine, coordinated by researchers from the Sant Pau Research Institute (IR Sant Pau)—who led two of the six studies—highlight the main technical, clinical, and regulatory challenges currently faced when integrating these biomarkers into daily clinical practice and adapting them to different healthcare settings. The goal is to make them truly useful, accelerate Alzheimer’s diagnosis, and improve global access to preventive and therapeutic treatments.
In this series, experts emphasize the transformative potential of biomarkers in advancing the diagnosis and treatment of Alzheimer’s disease, while also underscoring the complex challenges of integrating these tools into clinical practice and trials. Research on biomarkers—or biological indicators—for Alzheimer’s disease has traditionally focused on their sensitivity and specificity in diagnosing the pathology. However, in clinical practice, their utility will greatly depend on their positive and negative predictive value, which is significantly influenced by different healthcare settings.
One of the two papers led by IR Sant Pau, “Challenges in the practical implementation of blood biomarkers for Alzheimer’s disease,” highlights the challenges in implementing newly developed plasma biomarkers to detect this neurodegenerative disease and discusses the main limitations for their use in different settings, stressing the need for standardization to ensure accuracy and reliability of results.
“For example, in specialized or primary care, or in potential implementation in screening programs, among others. Some of these challenges are as basic as understanding the influence of preanalytical effects, such as how the sample is extracted and processed before the biomarker analysis itself,” explains Dr. Daniel Alcolea, researcher at the Memory Unit of IR Sant Pau and member of the Neurology Department at Hospital de Sant Pau. “Another challenge is understanding the influence of other diseases that may alter the interpretation of these markers’ results.”
The series of papers highlight two clinical practice scenarios where the importance of context in their use stands out. The first, addressed in the study led by Dr. Maria Carmona, researcher at the Memory Unit of IR Sant Pau and member of the Neurology Department at Hospital de Sant Pau, “Clinical and research application of fluid biomarkers in autosomal dominant Alzheimer’s disease and Down syndrome,” is the use of biomarkers in genetically determined forms of Alzheimer’s, such as early-onset autosomal dominant or Down syndrome. “Here, they are not so useful for diagnosing the disease, but rather help us understand what stage it’s in and monitor its progression.”
The second is the diagnosis of Alzheimer’s disease in populations with intellectual disabilities, one of the greatest challenges. In these individuals, symptoms may be masked by the underlying disability, and the use of reliable biomarkers can significantly improve diagnostic accuracy and facilitate access to disease-modifying therapies. This is especially important at a time when current diagnostic frameworks often exclude these populations.
Beyond the diagnostic realm, the six studies also emphasize the growing and crucial role of biomarkers in clinical trials, using them for appropriate participant selection, monitoring disease progression, and evaluating treatment efficacy. Biomarkers are essential tools that can significantly accelerate the development of effective treatments for Alzheimer’s and related dementias.
