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PubMed This is a summary of 24 peer-reviewed journal articles Updated
Neurology

What Is the Connection Between FTD and ALS? Explained

At a Glance

FTD and ALS are different conditions that can overlap in a minority of people because they share genetic and cellular pathways. Most people with FTD do not develop ALS; progressive weakness, swallowing, or breathing changes should be assessed promptly.

In this answer

3 sections

01

The FTD-ALS Spectrum

02

The Genetic and Biological Connection

03

Motor Symptoms to Watch For

When a doctor mentions Amyotrophic Lateral Sclerosis (ALS, also known as Lou Gehrig’s disease) during a conversation about Frontotemporal Dementia (FTD), it can be terrifying. You might wonder why a condition known for altering personality, behavior, or language is connected to a disease that causes progressive muscle weakness.

The most important thing to know right now: A doctor mentioning ALS does not mean you have it, and most people with FTD do not go on to develop ALS [1]. Doctors often mention ALS during an FTD diagnosis simply to explain routine monitoring, to ask about your family history, or because they are checking for all possibilities [2].

However, the reason they check is that researchers now understand FTD and ALS exist on a shared biological spectrum. While they are distinct clinical syndromes, a minority of patients experience an overlap between the two [3][4].

The FTD-ALS Spectrum

Historically, FTD (which primarily affects the brain’s frontal and temporal lobes) and ALS (which affects the motor neurons controlling muscles) were thought to be completely unrelated. Today, we know they can overlap clinically.

  • About 10% of people with FTD already show clinical signs of ALS when they are first diagnosed, and a small percentage (about 5%) develop ALS symptoms later on [1].
  • Conversely, while a smaller number of ALS patients develop full-blown FTD, up to half of people with ALS experience some degree of milder cognitive or behavioral impairment [5].

When a person meets the full diagnostic criteria for both conditions, doctors refer to it as FTD-ALS or ALS-FTD [3][6].

The Genetic and Biological Connection

For the subset of people who experience this overlap, the connection is deeply rooted in genetics and cell biology.

The C9orf72 Gene and Genetic Testing

The most common genetic link between FTD and ALS is a specific type of mutation (a “repeat expansion”) in a gene called C9orf72 [7]. When this gene is mutated, it can cause FTD, ALS, or both [7]. Remarkably, different people within the exact same family who carry this mutation can develop completely different conditions—one might develop behavioral FTD, while another develops ALS [8].

Carrying this mutated gene does not perfectly predict what disease a person will develop, how severe it will be, or when symptoms will begin [9][10]. Furthermore, not all FTD or ALS is caused by this gene; both conditions have other genetic and non-genetic causes [11]. If you have a family history of FTD, ALS, or unexplained dementias, it is important to speak with a genetic counselor. Standard genetic sequencing can sometimes miss the C9orf72 repeat expansion, so comprehensive panel testing guided by a professional is recommended [12].

The TDP-43 Protein

In healthy cells, a protein called TDP-43 lives inside the cell’s command center (the nucleus) and helps manage genetic instructions. In up to 97% of ALS cases and about 45% of FTD cases, this protein misbehaves—it escapes the nucleus and forms toxic clumps [13][14]. This specific malfunction is a major biological bridge between the two conditions [15]. It is important to note that TDP-43 presence is currently an autopsy or research finding, not a routine blood test you take at the clinic, and not all FTD cases involve TDP-43 (some involve different proteins like tau) [11].

Motor Symptoms to Watch For

Because of this connection, doctors monitor people with FTD for persistent, progressively worsening physical changes. Single, isolated symptoms—like a random muscle twitch or a cramp—are very common, have many benign causes, and do not mean you have ALS [16].

Doctors look for a pattern of progressive motor decline. If you or a caregiver notice the following, report them to your neurologist, who may use physical exams or tests like an EMG (electromyography) to find the cause [17]:

  • Muscle weakness or wasting: Slowly worsening, persistent weakness in a specific arm, leg, or hand, causing you to drop objects or trip frequently [18].
  • Fasciculations and cramps: Widespread, visible, rippling muscle twitches under the skin (fasciculations) combined with progressive weakness [16].
  • Stiffness and spasticity: Unusually stiff, tight muscles, or overly brisk reflexes (which a doctor can test) [19].
  • Bulbar symptoms (Mouth/Throat): Progressive changes in speech (slurring, hoarseness) or difficulty swallowing (coughing during meals) [20][21].

When to Seek Urgent Care

While most motor symptoms can be evaluated at a routine appointment, severe breathing or swallowing issues require immediate attention. Seek urgent or emergency care if you experience:

  • Severe choking or an inability to clear food or liquids from your throat [20].
  • Inability to swallow your own saliva [22].
  • New, severe breathlessness at rest or when lying flat [23].
  • A bluish tint to the lips or fingertips, indicating low oxygen [24].

Understanding the connection between FTD and ALS empowers you to advocate for comprehensive medical care, appropriate genetic counseling, and timely symptom management.

Common questions in this guide

Does a doctor mentioning ALS mean that I have ALS if I have FTD?
No. Doctors may mention ALS to explain routine monitoring, review family history, or evaluate possible causes, and most people with FTD do not develop ALS. A neurologist must assess the overall pattern of symptoms rather than a single twitch or cramp.
How are frontotemporal dementia and ALS connected?
FTD and ALS are different clinical conditions, but they can overlap in a minority of people and share some genetic and cellular pathways. C9orf72 repeat expansions and abnormal TDP-43 protein are important links, although not every person with FTD or ALS has either finding.
What symptoms could suggest an FTD-ALS overlap?
Doctors look for persistent, progressively worsening weakness, muscle wasting, or widespread twitches occurring with weakness. Stiffness, unusually brisk reflexes, slurred speech, hoarseness, or increasing difficulty swallowing can also require evaluation. An occasional isolated twitch or cramp is common and does not by itself indicate ALS.
Should I have genetic testing for the C9orf72 repeat expansion?
Genetic counseling can help determine whether testing is appropriate, especially when a family has FTD, ALS, or unexplained dementia. A comprehensive test guided by a genetics professional may be important because some standard sequencing methods can miss the C9orf72 repeat expansion.
When do swallowing or breathing problems require emergency care?
Seek urgent or emergency care for severe choking, inability to clear food or liquids, or inability to swallow saliva. New severe breathlessness at rest or when lying flat, or blue lips or fingertips, also requires immediate attention.
Can a routine blood test detect the TDP-43 changes linked to FTD and ALS?
TDP-43 clumping is currently mainly identified through research or examination of tissue after death, not through a routine blood test used in regular clinic care. Some FTD cases involve other proteins, such as tau, so TDP-43 is not present in every case.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What specifically made you mention ALS in my case—was it my family history, a specific physical symptom, or just routine monitoring?
  2. 2.Based on my symptoms and family history, do you recommend comprehensive genetic counseling and a panel test that specifically checks for the C9orf72 repeat expansion?
  3. 3.Would an electromyogram (EMG), breathing test, or swallowing assessment be useful right now to evaluate any of my physical symptoms?
  4. 4.If I begin to experience progressive muscle weakness or swallowing difficulty, what is the best way to contact the care team for a prompt evaluation?

Questions For You

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Related questions

Why Does Frontotemporal Dementia Cause Lack of Insight?How Is Frontotemporal Dementia Different From Alzheimer's?What Are the Symptoms of End-Stage Frontotemporal Dementia?How to Handle Aggression and Inappropriate Behavior in FTDWhy Does FTD Cause Hyperorality and Ritualistic Behaviors?Is Frontotemporal Dementia Hereditary? Genetic RiskWhat Are New Treatments for Frontotemporal Dementia?What Are Primary Progressive Aphasia (PPA) Symptoms?Why Aren't Alzheimer's Medications Usually Used for FTD?Why Is Frontotemporal Dementia (FTD) So Hard to Diagnose?

References

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This page explains the FTD–ALS connection for educational purposes and does not replace medical advice. A neurologist and genetic counselor can interpret your symptoms, family history, and testing.

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