NeuroVoices: Rebecca M. Edelmayer, PhD, on Advancing Blood Biomarkers in Alzheimer Disease for Earlier Diagnosis and Treatment Intervention

Rebecca M. Edelmayer, PhD

(Credit: X)

The accurate and timely diagnosis of Alzheimer disease (AD) remains a significant challenge in both primary and secondary care, in part because of limited and inconsistent access to diagnostic testing. Plasma phosphorylated tau (P-tau)217 has recently emerged as a promising blood-based biomarker for identifying AD-related neuropathologic changes. Previous studies have shown that plasma P-tau217 demonstrated a strong concordance with amyloid positron emission tomography and cerebrospinal fluid biomarker positivity, and is elevated in individuals with early symptomatic AD, including those with mild cognitive impairment (MCI) and mild dementia.¹ These findings suggest that plasma P-tau217 could serve as an effective tool for improving the accessibility, timeliness, and equity of AD diagnosis in clinical practice.

Moreover, research indicated that plasma P-tau217 may also play a role in identifying patients who are likely candidates for anti-amyloid immunotherapy.¹ With the increasing number of clinical trials focusing on P-tau217, a variety of assays are now in advanced stages of development or already available for clinical use. However, several critical questions persist regarding the current and future applications of this biomarker. Key areas that require further investigation include the standardization of assays, the establishment of minimum performance benchmarks, guidance on appropriate use, and the interpretation of results across diverse populations and in individuals with comorbid conditions. Additionally, considerations for the broader implementation and accessibility of plasma P-tau217 testing should be addressed to fully realize its potential in clinical practice.

Rebecca M. Edelmayer, PhD, vice president of scientific engagement at Alzheimer's Association, participated in a roundtable focused on the plasma P-tau217 assays at the recently concluded 2024 Clinical Trials on Alzheimer’s Disease (CTAD) conference, held October 29 to November 1, in Madrid, Spain.¹ In a new iteration of NeuroVoices, Edelmayer dived deeper into the role of blood biomarker tests for evolving AD diagnosis and treatment over the next few years. She spoke about the key challenges in integrating these tests into primary care settings and how the association’s upcoming clinical practice guidelines could potentially help clinicians better incorporate these diagnostic tools into their practice. Overall, Edelmayer spoke about the ways in which she envisions blood biomarkers to contribute to more equitable AD diagnosis and treatment globally.

NeurologyLive: How are these plasma assays currently being integrated into clinical practice for AD, and what impact have you observed on patient care with them?

Rebecca M. Edelmayer, PhD: The research on blood biomarker tests for AD is moving incredibly rapidly right now, and we're starting to see that these tests, when used by clinicians trained in diagnosing and treating memory disorders, can actually be quite effective in aiding the diagnostic process. They're not a standalone test and will never be one for AD. They need to be used in the context of a full clinical evaluation of patients. Currently, these tests are used when an individual comes to the doctor's office with some sort of memory or thinking concern. They serve primarily as a diagnostic tool, particularly for trained clinicians, but they are not being used to determine someone's risk for AD. For example, they aren't being used yet for individuals who are cognitively unimpaired but have a family history of the disease. We do believe these tools, the blood biomarker tests, will be incorporated more broadly across various clinical settings over time, but right now, they're mainly used in specialty care.

How do you think limitations of the biomarker tests could be addressed in the future to improve diagnostics and risk prediction?

Stepping back a bit, it’s important that as we try to implement these tools in clinical care, we have recommendations and guidance for clinicians on which patients are appropriate, which clinical settings are best, and we need evidence to support those recommendations. Currently, the Alzheimer's Association is working on developing a clinical practice guideline. This will be used not only by clinicians but also by policymakers and payers. Everyone involved needs this information to help guide how these tools are implemented in care. The clinical practice guidelines are being developed by a variety of subject matter experts and clinicians working in this space to determine how these tests should be incorporated into clinical care.

We’re evaluating all the evidence that exists today, which is primarily from research conducted in specialty care settings. However, we know that these tools could significantly change how we diagnose and treat AD in the future, especially in primary care settings. They could serve as a low-cost, non-invasive tool that may help confirm a diagnosis or even triage patients, referring them to specialty care. As we continue to develop these recommendations and guidelines, it's critical that they are evidence-driven. Clinicians must continue to publish research on the clinical utility of these tests across various settings, not just in terms of diagnosis, but also in how they add value to the treatment process for patients.

Is this something that clinicians should be on the lookout for in the future, these guidelines?

Yes, the guidelines from the Alzheimer’s Association are expected to be published in 2025. But it’s not just the guidelines that need to be published; the clinical tools, resources, and education will also be critical in informing how clinicians use these tools in their own practices. This will also be developed throughout 2025. One thing to note is that because things are moving so quickly, it will require an approach where the guidelines are more of a "living document" that can be updated regularly. As new clinical questions arise or new settings need to be addressed, clinical experts and subject matter specialists will evaluate the existing published evidence and help drive updated recommendations over time. These guidelines will continue to evolve as the science progresses.

Looking ahead, how do you envision these biomarkers playing a role in early detection and potentially treatment pathways?

That’s a big topic right now. We know that there are treatments available for individuals in the early stages of AD, and if prescribed at that stage, they are likely to have the most benefit in slowing disease progression. But this requires identifying and diagnosing individuals at an early stage of the disease. We do believe blood biomarkers will play a part in that diagnostic process. Again, they will never be a standalone test, but they will likely be an important component of ensuring individuals are offered new treatments as early as possible. We hope that these blood tests will become an accepted and equitable part of the diagnostic process, providing worldwide access to better care and early intervention.

Is there anything else you’d like to add regarding your participation in the roundtable or CTAD 2024 in general?

It’s been a really exciting time to be at CTAD. It’s amazing to see all of the science being presented, not just on diagnosis, but also on treatments and how that will transition into implementation and care in the future. As we continue to follow the AD and dementia space, I think it’s never been a better time to be a researcher in this field. I'm really happy to see that the Alzheimer's Association is not only funding much of the research presented here at the conference this year, but also playing a leading role in conducting some of that research as well.

Transcript edited for clarity. Click here for more coverage of CTAD 2024.

REFERENCES
1. Suárez-Calvet M, Braunstein JB, Beck R, et al. Plasma P-Tau217 Assays In Clinical Practice: Current Uses And Future Considerations For Diagnosing Alzheimer’s Disease. Presented at: 2024 CTAD; October 29-November 1; Madrid, Spain. LBRT1.