Current status of fluid biomarkers for early Alzheimer's disease and FDA regulation implications

Authors:  Angelo M. Jamerlan, Seong Soo A. An, John P. Hulme

Editor's Choice
Journal of the Neurological Sciences.  REVIEW ARTICLE| VOLUME 467, 123325, December 15, 2024

DOI: https://doi.org/10.1016/j.jns.2024.123325

Highlights

• Fluid biomarkers (e.g., Aβ, tau) have advanced AD diagnosis, with new ones being studied for early detection in CSF and blood.
• The FDA mandates that new LDTs follow in vitro diagnostics standards, possibly impacting innovation and development costs.
• Stringent LDT validation requires evidence for reliability, accuracy, and safety, possibly slowing AD biomarker advancements.
• Comparable oversight may arise globally, but significant variations in these standards may hinder their international adoption.
• Early FDA engagement, phased validation, and partnerships are encouraged to meet new demands while reducing delays and costs.

Many changes can now be seen in the development and use of tests, especially those incorporating fluid biomarkers, to diagnose Alzheimer's disease (AD), a devastating disease caused by the progressive but rapid degeneration of cortical tissue. Some biomarkers we already know have a significant association with AD, such as amyloid beta (Aβ) and tau, as well as the ratio of concentrations of other Aβ isoforms. In addition, several novel biomarkers are emerging that can also be used as diagnostic fluid biomarkers for AD, but many studies are still needed before we can consider them reliable.

The U.S. Federal Food and Drug Administration recently announced its final ruling to regulate laboratory-developed tests (LDTs) as medical devices, which can significantly impact LDT development. In this narrative review, we discuss the current status of fluid biomarkers used to diagnose early AD, their potential and limitations, and the impact caused by the FDA's decision and strategies to help developers navigate the complex changes in the regulatory landscape of LDTs.