Back to News and Events

Disease Connections: FTD, ALS, and Alzheimer’s

Research to help us better understand how FTD, ALS, and Alzheimer’s disease are connected will lead to more effective ways to diagnose, treat, and ultimately cure degenerative brain diseases.


At the American Brain Foundation, we know that when we discover the cure for one brain disease, we will cure many others. This approach to research comes from our knowledge that all brain diseases are connected. Current research in the area of neurodegenerative diseases offers a prime example of how these connections help us better understand the causes, progression, and potential treatments for a range of diseases.

Below we explore some of the connections between several types of neurodegenerative diseases that result in dementia and cognitive decline: Alzheimer’s disease and ALS-FTD spectrum disorders.

What Is Alzheimer’s Disease?

Dementia is a general term for memory loss and other serious cognitive and behavioral changes that affect a person’s daily life. There are multiple types of dementia, and different diseases can cause dementia at various stages. Alzheimer’s disease is the most common type of dementia, accounting for 60 to 80% of all cases. 

Alzheimer’s disease is characterized by progressive memory loss beyond what is expected with normal aging. It is caused by buildups of misfolded proteins in the brain, which damage the surrounding tissue and disrupt communication between the nerves in different parts of the brain. Because the primary cognitive symptoms of Alzheimer’s do not appear until well after the disease has started, it is very difficult to diagnose and treat.

What Are Frontotemporal Disorders (FTD)?

Frontotemporal disorders (FTD) are a group of neurodegenerative disorders associated with changes in the brain’s frontal and temporal lobes, which control functions related to personality, behavior, and language. People with FTD experience shrinking of these lobes, as well as the buildup of certain proteins in the brain. In some cases, FTD has been linked to genetic mutations, but more than half of people with FTD have no family history of the disease.

A person’s specific symptoms and the order in which they appear will vary from case to case, often depending on which areas of the brain are affected. Generally, changes in the frontal lobe affect behavior while changes in the temporal lobe affect language and emotions. These changes could lead to impulsive, apathetic, socially inappropriate, and/or repetitive compulsive behavior, or problems with language or loss of speech. Cases marked by primarily cognitive, language, and memory symptoms are sometimes referred to as frontotemporal dementia (also known as Pick’s disease). 

What Is ALS?

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease that attacks the nerve cells in the brain and spinal cord that control voluntary muscle movement. As these nerve cells are damaged and eventually die, they stop sending messages to muscles throughout the body, causing the muscles to weaken, twitch, and deteriorate. 

The main symptoms of ALS include muscle weakness, stiffness, and atrophy. As the disease progresses, people with ALS have difficulty standing, moving, walking, swallowing, and speaking. Eventually, they lose the ability to breathe without a ventilator.

The disease is caused by a decline in motor neuron function, but it’s not yet clear why this occurs in some people and not others. In 90% to 95% of cases, the cause of ALS is sporadic, meaning there is no clear cause, risk factor, or family history. 

Types of Dementia: FTD vs. Alzheimer’s Disease

Dementia is linked to a buildup of proteins that damage and kill nerve cells in the brain. The clumping of different types of protein lead to different types of dementia. For example, in people with Alzheimer’s, beta-amyloid proteins build up between nerve cells and tau proteins accumulate inside nerve cells. Abnormal accumulations of tau, TDP-43, and FUS proteins are commonly linked to FTD, while abnormal alpha-synuclein proteins are associated with Lewy body dementia

There are also some differences between the symptoms of Alzheimer’s disease and the dementia that results from frontotemporal disorders. Symptoms of FTD typically appear earlier in life—between ages 40 and 65—and Alzheimer’s disease usually develops after age 65. Memory loss is more prominent in early Alzheimer’s than early FTD. Behavioral changes are usually the first symptom of the most common form of FTD and tend to occur later in Alzheimer’s. Issues with spatial orientation are more common with Alzheimer’s, while speech problems are more common with FTD.

These similar mechanisms and overlapping symptoms create targeted opportunities for research. While different types of dementia each have their own specific causes, identifying how to treat the harmful protein buildups responsible for one of these diseases will aid in the treatment of all the others. 

The ALS-FTD Spectrum

FTD and ALS share some genetic characteristics and may share common causes in some cases. In 2011, researchers discovered that the C9orf72 gene mutation can cause both ALS and FTD, and other genes have also been identified to play a role in both diseases. Research has also found that in most people with FTD and ALS, deposits of a protein called TDP-43 accumulate in nerve cells.

Rather than two distinctly separate diseases, researchers are beginning to think in terms of an ALS-FTD spectrum, with diagnoses depending on whether movement–based or cognitive symptoms appear first.

As researchers learn more about the genetics, causes, and symptoms of ALS and FTD, those insights provide a better understanding of both diseases and can aid in the development of more effective treatments.

Can ALS Cause Dementia?

ALS itself is not known to be associated with cognitive impairment or have a direct link to Alzheimer’s disease specifically. But studies show that as ALS progresses, some people develop a form of dementia that presents as FTD. Research shows that as many as 50% of people with ALS develop cognitive and/or behavioral impairment, with 20% meeting criteria for a dementia diagnosis. The other half of people with ALS do not develop these symptoms. On the other hand, about 30% of people with FTD develop motor problems associated with ALS.

Current Neurodegenerative Disease Research

By investing in research across all neurodegenerative diseases, we increase the chances of finding key insights that will apply to more than one disease. 

The American Brain Foundation is currently funding multiple researchers looking into ALS-FTD spectrum disorders, including Marina Avetisyan, MD, PhD, and Sanjana Shellikeri, PhD. Eva Klinman, MD, PhD, is investigating the broad mechanisms behind neurodegenerative diseases like Alzheimer’s—research that may yield additional insights into the formation of FTD and other dementias.

The American Brain Foundation’s Cure One Cure Many Award supports research to find a biomarker for the early diagnosis of Lewy body dementia. Finding a biomarker (diagnostic test) for Lewy body dementia would help distinguish it from other dementia disorders and offer clues for effectively diagnosing diseases like Alzheimer’s and FTD.

As we pursue research into ALS-FTD and Alzheimer’s disease, we have the potential to contribute to greater breakthroughs across many different neurodegenerative diseases. These research insights will lead to new or improved treatments, better diagnosis methods, and ultimately cures for a range of brain diseases.

The American Brain Foundation knows that when we find the cure to one brain disease, we will find cures to many others. Learn more about the brain disease research we fund, or donate today to support the cures and treatments of tomorrow.