FTD lies at the genetic and symptomatic intersection of a number of neurodegenerative disorders. One of them is amyotrophic lateral sclerosis (ALS). A variant in the C9orf72 gene is the most common cause of both genetic FTD and ALS, and both FTD and ALS can present within the same family, or even in the same person, a condition known as FTD-ALS. While less common, variants in other genes can also cause both FTD and ALS, including VCP, FUS, TARDBP, SQSTM1, TBK1, CCNF, CHMP2B, OPTN, TIA1, and CHCHD10 (Kirola, Mukherjee, & Mutsuddi, 2022).

FTD and ALS can present with a combination of motor and cognitive symptoms. In addition to the changes in behavior, personality, and language skills that are common as FTD symptoms, individuals with FTD-ALS may have difficulty walking, standing, using their hands, speaking, swallowing, or breathing.

Apparently sporadic cases of FTD-ALS can also occur, and sporadic FTD caused by TDP-43 proteinopathy resembles the molecular pathophysiology of ALS. People with C9orf72 expansions are particularly at risk for developing both FTD and ALS symptoms, regardless of which clinical syndrome initially presents (Spencer et al., 2024).

Despite these shared characteristics, clinical care between FTD and ALS is often siloed. Depending on the first presenting symptoms, or which clinical syndrome has predominated in a family, people impacted by the FTD-ALS spectrum may be seen by behavioral neurologists or by movement specialists. Clinical care can differ significantly between these specialties; genetic testing, for example, is standard clinical practice for ALS, but not typically offered for people with FTD (Jenny, et al., 2024). This bifurcation in clinical care can result in diagnostic delays, gaps in access to treatment, and lack of awareness of research opportunities.

While prevalence rates vary, it appears that at least half of people with ALS have FTD-like cognitive symptoms, and a subset of those meet diagnostic criteria for FTD (Cividini et al., 2022; Ferrari et al., 2013). In 2021, AFTD and the FTD Disorders Registry collaborated on the FTD Insights Survey to better understand FTD disorders from the perspective of persons diagnosed, family members, and care partners. In the survey, 73 respondents (including 63 care partners and 10 persons diagnosed) described their experiences with FTD-ALS.

Respondents reported numerous challenges obtaining a timely diagnosis of FTD-ALS, due in part to the heterogeneity of its presenting symptoms. Most respondents were initially given a misdiagnosis, including depression (32%), anxiety (22%), and Alzheimer’s disease (12%). An overwhelming majority (86%) needed to see more than three doctors before getting diagnosed with FTD-ALS, and 18% saw more than five.

Respondents pointed to a wide range of first signs that something was wrong, including changes in personality, thinking, motor skills, mood, language, memory, and sleep. The symptoms they found most distressing varied. Care partners cited changes in their loved one’s personality (30%), changes in their loved one’s mood (14%), and “other” symptoms, defined as reduced motor skills, relationship problems, sleep issues, delusions/hallucinations, and/or a specific difficulty in everyday life (33%). Persons diagnosed, meanwhile, were most distressed by language symptoms (34%) and other symptoms (22%). Additionally, 22% reported not being distressed by any symptoms. As is often seen in FTD disorders, many care partners (specifically, 30% of those surveyed) reported that the person diagnosed with FTD-ALS was not aware of their symptoms at all, or only aware just a little bit.

Asked what they would most value in a treatment for FTD-ALS, approximately two out of three respondents (67%) said they’d want it to improve their independence. Clear majorities said they would like a treatment to help them better communicate (64%), improve the quality of relationships (63%), and control their emotions and behavior (56%); and 21% said they would like a treatment that gave them the ability to hold a job.

Though this survey was based on a small sample size, healthcare providers treating people with FTD, ALS, and related conditions should be aware of the range of symptoms experienced by these groups, and how those symptoms affect their daily lives (Dodge et al., 2024). Professionals can request and explore additional data by visiting the FTD Disorders Registry website.

FTD and ALS healthcare providers should stay aware of emerging clinical trial opportunities. Providers often serve as gatekeepers to research recruitment. People with FTD consider their clinicians’ opinions to be one of the most important factors in deciding whether to try a new treatment (Association for Frontotemporal Degeneration, 2021). They typically have ongoing relationships with, and a high degree of trust in, their providers, which are essential elements in making decisions about research participation (Taft et al., 2019).

Recent basket trials, such as those focused on C9orf72, have been including persons diagnosed with both FTD and ALS, and biopharmaceutical companies are looking to grow their ALS programs to include people currently living with FTD as well as those at genetic risk of developing it. Knowing the challenges of navigating the constantly shifting clinical trial landscape, the FTD Disorders Registry – leveraging a recent platform upgrade – continues to centralize research resources for people impacted by all FTD disorders and aggregate information about participating in research.

Fortunately, many clinicians, researchers, and advocates recognize the need for synergy between the FTD and ALS fields. In recent years the International Symposium on ALS/MND, the biggest annual conference dedicated to ALS and motor neuron disease research, has included sessions dedicated to the overlap between FTD and ALS. Likewise, the 2024 International Conference on Frontotemporal Dementias included a workshop on the FTD and ALS spectrum co-organized by Drs. Corey McMillan, Michael Benatar, and John van Swieten and sponsored by AFTD and others. The Barrow Neurological Institute has also spearheaded a C9orf72 FTD-ALS workshop, started in 2023 and reconvening in 2025, focused on breaking down silos between the FTD and ALS fields. Genetic ALS & FTD: End the Legacy is a patient-led organization dedicated to the needs and interests of the genetic ALS and FTD community, and co-sponsored (with AFTD and other groups) a 2023 workshop offering guidance for pre-symptomatic genetic FTD and ALS.

AFTD has been working with other groups on ways to decrease fragmentation in the field, facilitate the expansion of ALS clinical trials into FTD, and ensure that the breadth of FTD and ALS experiences are represented in key conversations. In 2024, AFTD partnered with the ALS Association on a C9orf72 FTD/ALS Prevention Trial workshop. Organized by Drs. Michael Benatar and Adam Boxer, the one-day meeting convened FDA staff with FTD and ALS experts (clinicians, researchers, people with lived experience) to discuss what would be needed to design a C9orf72 prevention clinical trial. AFTD is also the sole FTD-focused member of the Accelerating Medicines Partnership for ALS (AMP ALS), which aims to accelerate the discovery of new biomarkers and targets for interventions for ALS. Launched by the Foundation for the National Institutes of Health, AMP ALS is a precompetitive consortium that includes federal agencies, nonprofits, and biopharmaceutical companies among its partner organizations.

AFTD works to share FTD care, support, and research resources with ALS professionals, and continues to develop innovative ways to achieve that goal. AFTD’s 2025 Annual Education Conference will include, for the first time, a half-day Genetic FTD Symposium, as well as a plenary discussion with leading FTD and ALS experts on bridging the gap between these diseases. If you’re a healthcare provider interested in learning more about how AFTD can support you in better understanding FTD and ALS, please contact AFTD’s HelpLine at 866.507.7222 or info@theaftd.org.