Familial Frontotemporal Dementia: How Is FTD Inherited?

Frontotemporal Dementia (FTD) is a group of disorders primarily impacting the frontal and temporal lobes of the brain. In this article, we will explore the genetic link associated with FTD, its definitions, available treatments, and the diagnostic tools currently in use or under development, including the promising field of fluid biomarkers and neuroinflammatory markers in both blood and cerebrospinal fluid (CSF).
Frederika Malichová

Frederika Malichová

Neuroscientist at the University Of Cambridge.

A drawing of a brain and a DNA helix.

Frontotemporal Dementia: An Overview

FTD is caused by an accumulation of either tau, TDP-43 or FUS proteins in the frontal and temporal lobes of the brain.

It leads to significant changes in behavior, personality, and language abilities.

Frontotemporal dementia often emerges in individuals during their 40s to 60s, making it a leading cause of dementia in this age range.

It can be categorized into several subtypes, including:

  • behavioral variant FTD (bvFTD),
  • semantic variant primary progressive aphasia (svPPA)
  • non-fluent variant primary progressive aphasia (nfvPPA),

Each is characterized by distinct clinical features and underlying neuropathological changes. We took a closer look at the symptoms of FTD in our blog about the 7 stages of Frontotemporal Dementia.

FTD can appear sporadically, but around 30-40% are inherited. This form is known as Familial Frontotemporal Dementia (fFTD) [1,2,3,4].

Familial Frontotemporal Dementia is a hereditary condition caused by mutations in specific genes.

It is passed down within families, and affected individuals have a 50% chance of passing the mutated gene to their offspring.

Several genes have been identified as being associated with familial frontotemporal dementia. The most common ones include [3,4,5,6]:

1. C9orf72 Gene:

  • Prevalence: Mutations in the C9orf72 gene are the most common and well-recognized genetic cause of familial frontotemporal dementia.
  • Associated Conditions: This gene is not only implicated in frontotemporal dementia but is also a major genetic factor in Amyotrophic Lateral Sclerosis (ALS), often referred to as ALS-FTD. This overlap highlights the genetic complexity of neurodegenerative diseases.
  • Pathological Mechanism: The C9orf72 mutation leads to the accumulation of abnormal repeat expansions of nucleotide sequences in the gene. These expanded repeats are thought to contribute to the development of both frontotemporal dementia and ALS, although the exact mechanisms are still under investigation.

2. MAPT Gene:

  • Subtype Association: Mutations in the MAPT gene are primarily associated with a specific subtype of familial frontotemporal dementia known as FTD with tau pathology.
  • Tau Protein Abnormalities: Tau is a microtubule-associated protein that plays a crucial role in maintaining the structural integrity of nerve cells. Mutations in the MAPT gene lead to abnormalities in tau protein, resulting in the formation of tau aggregates or tangles in the brain. These tau tangles are characteristic pathological features of frontotemporal dementia with tau pathology.

3. GRN Gene:

  • Subtype Association: Mutations in the GRN gene are linked to another subtype of familial frontotemporal dementia, often referred to as frontotemporal dementia with TDP-43 protein pathology.
  • TDP-43 Protein Abnormalities: The GRN gene provides instructions for producing progranulin, a protein that is involved in cell growth and maintenance. Mutations in GRN lead to a reduction in progranulin levels, which, in turn, cause abnormal accumulation of another protein called TDP-43 within nerve cells. TDP-43 proteinopathy is a common hallmark of frontotemporal dementia.

Diagnostic Tools for Frontotemporal Dementia

Early diagnosis of frontotemporal dementia is crucial for providing appropriate care and support.

There are several diagnostic tools that can be used to assess and diagnose both sporadic and familial frontotemporal dementia [4,6,7,8].

These are summarized in the following MediSearch query:

In the case of familial FTD, genetic testing is another crucial diagnostic tool. Try asking MediSearch a question about genetic testing and familial FTD in the above window!

Diagnostic Tools in Progress:

Researchers are continually exploring new diagnostic tools and ways to diagnose FTD more accurately [4,6,9,10].

  1. Biomarker Research: Various biomarkers associated with FTD such as tau and TDP-43 have been studied. Detecting these biomarkers in cerebrospinal fluid (CSF) or through neuroimaging techniques like positron emission tomography (PET) scans can aid in more accurate FTD diagnosis.
  2. Blood-Based Biomarkers: Research has been ongoing to identify blood-based biomarkers for FTD. These markers, if validated, could provide a less invasive and more accessible means of diagnosing and monitoring the disease.
  3. Digital Biomarkers: With the increasing use of wearable devices and smartphone apps, researchers have been exploring the potential of digital biomarkers. These technologies can monitor subtle changes in behaviour, cognition, and daily activities, which may help in early FTD detection and tracking disease progression.
  4. Neuroimaging Techniques: Advanced neuroimaging methods, such as functional MRI and diffusion tensor imaging, are being explored to detect specific patterns of brain atrophy and connectivity alterations associated with FTD. These techniques can provide valuable insights into the structural and functional changes in the brain.
  5. Machine Learning and AI: Artificial intelligence and machine learning algorithms have been applied to analyze large datasets of clinical and neuroimaging information. These algorithms have the potential to improve diagnostic accuracy by identifying unique patterns and markers that may not be readily apparent to human clinicians.
  6. Genetic Testing Advances: Genetic testing for FTD-related mutations has become more accessible and affordable. Continued research in genetics is helping identify novel FTD-related genes and mutations, enhancing our understanding of the genetic underpinnings of FTD.
  7. Multi-modal Approaches: Combining multiple diagnostic approaches, including clinical assessment, neuroimaging, genetic testing, and biomarker analysis, can provide a more comprehensive and accurate diagnosis of FTD.

Treatment Options

Currently, there is no cure for familial FTD, but several treatment strategies aim to alleviate symptoms and improve the quality of life for affected individuals [4,11,12,13].

These treatments may include:

  1. Medications to manage behavioural symptoms, such as antidepressants and antipsychotic drugs.
  2. Speech therapy, occupational therapy, and physical therapy to address communication and functional impairments.
  3. Supportive care and counselling for both patients and their families.


Familial Frontotemporal Dementia is a complex condition with a strong genetic link. Understanding the associated genes, available treatments, and diagnostic tools is crucial for both affected individuals and their families. continues to advance, there is hope for earlier and more accurate diagnosis, ultimately improving the management of this devastating disease. You can stay informed about the latest developments in familial FTD research to better navigate this challenging condition using MediSearch.

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Frederika Malichová

Frederika Malichová

Frederika is a postgraduate researcher at the University of Cambridge, where she investigates new biomarkers for Frontotemporal Dementia and other tauopathies. Her research has been published at prestigious conferences such as the Alzheimer’s Association International Conference 2023. She obtained her BSc in Biomedical Sciences from UCL, where she worked closely with the UK Dementia Research Institute.