FTD researchers know the importance of identifying and validating usable biomarkers for FTD – and just how complex these tasks are. 

FTD-specific biomarkers could help to achieve many unmet needs for families and researchers: improved diagnostic accuracy and sensitivity, improved prognosis prediction, identification of which people suffer from which types of pathology, and accelerated drug development (by more accurately measuring treatment responses).  

Thanks to the guidance of our Medical Advisory Council, AFTD has long recognized the lack of biomarkers as a critical gap. 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. 

Progress Made in Biomarkers Research  

Progress has been notable. Dr. Leonard Petrucelli, Dr. Tania Gendron, and colleagues identified CSF poly(GP) as a target engagement biomarker for drug development for ALS/FTD. Dr. Anthony Fitzpatrick and colleagues identified TMEM106B fibrils in FTD (and other neurodegenerative diseases) with TDP-43 pathology, raising prospects of rationally designed PET ligands. Building on years of multicenter international natural history studies in FTD (ALLFTD and GENFI), the FTD Prevention Initiative published disease progression models with integrated fluid and imaging biomarker data to guide clinical trial design. These and other emerging tools offer hope for the field.  

AFTD was also an inaugural member of the Alzheimer’s Drug Discovery Foundation (ADDF) Diagnostics Accelerator, a collaborative program with Gates Ventures to fund the development of biomarkers for Alzheimer’s and related dementias. Through AFTD’s partnership, the ADDF Diagnostics Accelerator awarded $3.2 million for five FTD biomarker development programs.  

Examples of key grants included the Neurofilament Surveillance Project, started by the Bluefield Project to Cure FTD in 2019 to accelerate neurofilament light (NfL) research; a second grant was awarded in 2021 to Dr. Rohini Khillan  at the Foundation for the National Institutes of Health (FNIH), to study NfL as a fluid biomarker. In 2024, the FNIH Biomarker Consortium announced that the U.S. Food and Drug Administration (FDA) accepted its letter of intent to qualify NfL as a biomarker for the early detection of genetic FTD. Thanks to these and other important programs, the field of FTD biomarker development has matured.  

Despite the progress, many gaps remain. Until biomarkers are developed to reliably distinguish between cases of TDP-43, tau, and FUS pathology, drug development for FTD will remain focused on genetic forms of disease. Similarly, expanded identification and validation of target engagement and response biomarkers for clinical trials will improve go/no-go decision-making after Phase 2 clinical trials, and likely inform regulatory decision-making for new drug approvals.  

These gaps and others were reviewed in the 2023 Holloway Summit, an annual program 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 current state of science and the need for validated FTD biomarkers. The 2024 AFTD Research Roundtable also focused on biomarkers, with emphasis on their central role in clinical trials and drug development. The meeting included insights from regulatory experts at the FDA and European Medicines Agency, 15 biopharma members focused on FTD drug development, and academic scientists, advocates, and nonprofit representatives.  

Enthusiasm for cryptic exon and exosome biomarkers is widespread. For these and other emergent biomarkers to be used outside of exploratory research, the assays must be developed to be scalable and reliable across laboratories, with both analytical and clinical validation.  

While the discovery of new biomarkers remains important, the field must also prepare for the validation work needed for emerging biomarkers to be used in either clinical care or regulatory-grade clinical trials, or in clinical care. The FNIH Neurofilament Light qualification working group has received feedback from the FDA on the clinical, analytical, and statistical feedback needed to increase confidence in use. Such feedback was reviewed at the FTD Research Roundtable as an example of the type of work anticipated as needed for exploratory biomarkers to be validated for clinical and regulatory use.   

Diagnostic Biomarkers: An Especially Urgent Need  

Despite significant progress, proper diagnostic tools that can accurately detect FTD early remain an ongoing need. Survey data from the FTD Disorders Registry indicates that it takes an average of 3.6 years to receive an FTD diagnosis. This figure is undoubtedly an underestimate, as it was sampled from families who have received the correct diagnosis and have connected with AFTD. 

The complex symptomology of FTD can create considerable challenges for clinicians due to their overlap with other behavioral, psychiatric, and neurodegenerative disorders. FTD is often misdiagnosed, often multiple times, which delays vital interventions that could maximize quality of life for the person with FTD.  

All who are diagnosed with FTD experience the disorder differently, with a person’s cultural background changing how symptoms present and how they may be recognized by others; however, many existing diagnostic tools lack adaptations for non-western cultures. Combined with the socioeconomic barriers that can restrict access to healthcare, people from diverse backgrounds, underserved communities, and those below the poverty line often face significant challenges with FTD diagnosis. As illustrated by a piece recently published in the New York Times about Linde Jacobs, a genetic carrier for FTD and advocate whose mother was incarcerated due to her symptoms, the criminal justice system is poorly equipped to handle the disorder. AFTD recently put out a webinar to educate health professionals on the interaction between FTD and the criminal legal system. 

AFTD Releases Request for Proposals for New FTD Biomarker Initiative 

AFTD is launching a new funding program to identify diagnostic biomarkers for FTD. People with lived experience in FTD provided invaluable feedback on the biggest challenges in their diagnostic journey to shape the priorities of this program.  

This program is made possible by the AFTD Holloway Family Fund, the Alzheimer’s Association, and additional funding partners who have a shared mission to improve access to diagnosis for all people with FTD.  

“Too many families struggle for years without an FTD diagnosis, which also hinders research progress. 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,” said AFTD Board Member Kristin Holloway.  

“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 marks 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,” Dr. Snyder continued. 

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, with guidance from the AFTD Medical Advisory Council.   

AFTD invites applications to address the significant gaps illustrated in this article with research studies focused on the discovery, validation, and/or development of scalable, accessible diagnostic tools to help screen and diagnose FTD disorders. This initiative aims to advance diagnostic precision, improve early detection, and enhance patient outcomes by supporting innovative and impactful research projects. 

AFTD will consider proposals that include, but are not limited to: 

• Identification of novel biomarkers (e.g., molecular, imaging) for FTD in biological samples such as blood, cerebrospinal fluid, saliva, or tissues.    

• Evaluation of low-cost screening biomarkers to shorten the path to diagnosis (e.g., a biomarker that could identify neurodegeneration and thus lead to a neurologist consultation versus a psychiatrist).  

• Replication studies to validate the utility and reliability of identified biomarkers.    

• Development of standardized assays or protocols to quantify biomarker levels.     

• Translation of biomarkers into clinically applicable diagnostic tools.    

• Integration of multi-modal approaches (e.g., combining imaging and molecular data) to enhance diagnostic accuracy. 

The initiative is open to investigators worldwide at academic or other nonprofit research institutions, as well as those at for-profit organizations such as biotechnology firms.  

AFTD Online Submission Portal Opens: March 2025 

Proposal Submission Deadline: May 9, 2025
Award Announcements: Late summer/early fall 2025

For more information about AFTD’s request for proposals, visit the FTD Biomarkers Initiative page on our website. 

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