Biomarkers are critical to understanding and treating any disease. A biomarker is something measurable in the body that can indicate a disease’s presence and severity. High blood pressure, for example, is a biomarker that can indicate whether a person has heart disease and how serious it is: the higher the blood pressure numbers, the more progressed or severe their disease.

Biomarkers can be used for different purposes. Diagnostic biomarkers distinguish one disease from another, contributing to accurate and timely diagnosis, which is necessary for targeted treatments, services, and support options. Prognostic biomarkers help clinicians predict how a disease will progress – for example, by detecting a genetic factor associated with more aggressive acceleration of disease. Monitoring biomarkers indicate if a disease is worsening or improving, and response biomarkers used in research can determine if an experimental treatment is having its intended effect. Additional biomarkers can indicate the risk of future disease, or the safety of a treatment.

All biomarkers are critical to understanding what is going on in the body at a moment in time – to inform targeted clinical care, research, and support.

Despite their recognized importance, biomarkers are not easy to identify and validate. Indeed, while FTD research has begun to identify promising potential biomarkers, some of which have begun to be used in clinical trials, the search for validated FTD biomarkers continues. Even for common diseases, it can take decades and significant funding to identify usable biomarkers.

The process takes so long because biomarkers need to be validated for each clinical use and require extensive data documenting that researchers and clinicians can both reliably quantify and clinically interpret the biological measure. Biomarker development relies upon volunteers willing to participate in research, alongside the latest technological advances and leading-edge study design and data-analysis methods.

AFTD has long recognized biomarker identification as a critical gap in FTD research and has directly funded research in this area. From 2016 to 2021, AFTD disbursed $5 million in research funds to 16 biomarker-focused projects through the FTD Biomarkers Initiative made possible by the Samuel I. Newhouse Foundation. This program enabled many advances, such as improved brain imaging techniques, structural information on protein aggregates common in FTD pathology, building of disease progression models used to inform clinical trials, and more.

AFTD was also an inaugural member of the Alzheimer’s Drug Discovery Foundation (ADDF) Diagnostics Accelerator, a collaborative funding program initiated by ADDF co-founder Leonard A. Lauder, Bill Gates, Jeff Bezos, MacKenzie Scott, the Dolby family, and the Charles and Helen Schwab Foundation to develop novel biomarkers for the early detection of Alzheimer’s disease and related dementias. With AFTD’s partnership, again made possible by the S.I. Newhouse Foundation, the Diagnostics Accelerator awarded $3.2M for five FTD biomarker development programs.

One key investment was the Neurofilament Surveillance Project (NSP), led by the Bluefield Project to Cure FTD. This pioneering multiyear study leverages the infrastructure of the ALLFTD natural history study and the support of companies and nonprofits to develop the biomarker neurofilament light (NfL) into a tool acceptable for use in regulatory-grade clinical trials.

Another key investment was the Foundation for the National Institutes of Health’s Biomarker Consortium, also on NfL. In this project, companies and nonprofits are partnering with scientific leaders to strengthen the evidence for the use of NfL to enable clinical trials to delay or prevent disease onset in people at genetic risk of FTD. In 2024, the Consortium announced that the U.S. Food and Drug Administration accepted its letter of intent and provided feedback on further steps to qualify NfL as a biomarker for the early detection of genetic FTD.

Feedback from these projects was reviewed at the 2024 AFTD Research Roundtable, where stakeholders discussed the steps they anticipate will be needed for emergent biomarkers to be ready for use in drug approvals. (AFTD has convened the FTD Research Roundtable each year since 2023; it is made possible by the collaborative support of government regulators from the U.S. and Europe, drug development companies, academic scientists, nonprofits, and persons with lived experience, all committed to accelerating progress towards treatments for FTD.)

Despite significant progress, tools that support early, accurate diagnosis remain a persistent and urgent need. Survey data from the FTD Disorders Registry indicates that it takes an average of 3.6 years to receive an FTD diagnosis. This staggering figure is nevertheless an underestimate, as it represents the experience of families who have been able to get access to the care needed to receive the diagnosis at all.

Primary care settings lack affordable screening tools to prompt patient referrals to the specialists needed for an accurate FTD diagnosis. Due to overlapping symptoms with other diseases, and healthcare professionals’ lack of familiarity with FTD, misdiagnosis and delayed diagnosis are both common. Repeated specialist visits cost time and resources, impeding diagnosis for many people. For these reasons, AFTD is actively working to increase recognition of FTD and decrease obstacles to obtaining correct and timely FTD diagnoses.

Access to diagnosis can be even more challenging for people of diverse backgrounds, socioeconomic groups who are underserved, homeless people, and people with interactions with the criminal justice system. A poignant piece published in the New York Times about Linde Jacobs, a genetic carrier for FTD and an FTD advocate, illustrates her mother’s challenges with diagnosis and how the criminal justice system is not yet capable of handling persons diagnosed. AFTD recently conducted a webinar to educate health professionals on the interaction between FTD and the criminal legal system.

The potential of biomarkers to improve access to diagnosis in FTD was a focus of discussion at the 2023 AFTD Holloway Summit. The Holloway Summit is an annual program hosted by Kristin Holloway and generously funded by the Holloway Family Fund. The 2023 Summit convened clinicians, scientists, drug developers, nonprofit partners, and people with lived experience of FTD to review the state of the science and the need for FTD biomarkers.

Diagnostic biomarkers are necessary not only to shorten the diagnostic journey, but to increase the number of people identified with FTD, where strength in numbers improves advocacy, research participation, fundraising efforts, and all other strategies for improving the lives of people touched by this disease. For these reasons, diagnostic biomarker identification is a cornerstone of AFTD’s commitment to advance the research that will one day usher in a future free of FTD.

AFTD is launching a new funding program to develop diagnostic biomarkers for FTD as part of our mission to improve diagnoses across these and related disorders. People with lived experience in FTD helped to shape the goals of this program by providing invaluable feedback on the biggest gaps in their diagnostic journeys.

This program is made possible by the AFTD Holloway Family Fund, the Alzheimer’s Association, and other partners dedicated to improving access to diagnosis for all people with FTD.

“Too many families struggle for years without an FTD diagnosis, which also hinders research progress,” said AFTD Board Member Kristin Holloway. “It is clear that investing in diagnostic biomarkers for FTD is one of the most critical steps we can take toward improving care and accelerating treatments for this devastating disease.

“Through the Holloway Family Fund, we are proud to support this initiative, which will help researchers develop the tools needed for earlier and more accurate diagnosis – bringing hope to individuals and families facing FTD,” she continued.

“It’s critically important to have tools for early and accurate detection of all causes of dementia, said Heather Snyder, PhD, Alzheimer’s Association Senior Vice President of Medical and Scientific Relations. “That’s why the Alzheimer’s Association is proud to partner with the AFTD Holloway Family Fund and other partners to fund high-risk, high-reward projects to advance our ability to detect and diagnose frontotemporal lobar degeneration. This funding program and partnership mark how far the field has come in both the understanding of the underlying biology, but also the technology to be able to measure this biology in people.”

In the program’s first round, over $1 million will be made available for two to four research projects. A second round of awards is anticipated in 2026. Research proposals will be competitively evaluated for funding, thanks to the guidance of the AFTD Medical Advisory Council.  Successful applications will have a clear vision of how the biomarkers of interest will improve the diagnostic journey of those with FTD.

AFTD will keep our community informed of progress as this new program unfolds. As always, we thank our generous donors and funding partners. And we thank the research participants for sharing their data and tissue samples. Advancing the discovery of FTD biomarkers is one of our primary research focuses, and significant strides are being made. Without all of you, none of this progress would have been possible.

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