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Related Dementias

Causes of Frontotemporal Disorders

Frontotemporal lobar degeneration (FTLD) is not a single brain disease but rather a family of brain diseases that share some common molecular features. Scientists are beginning to understand the biological and genetic basis for the changes observed in brain cells that lead to FTLD.brain scan

Scientists describe FTLD in terms of patterns of change in the brain seen in an autopsy after death. These changes include loss of neurons and abnormal amounts or forms of proteins called tau and TDP-43. These proteins occur naturally in the body and help cells function properly. When the proteins don’t work properly, for reasons not yet fully understood, neurons in specific brain regions are damaged.

In most cases, the cause of a frontotemporal disorder is unknown. In about 15 to 40 percent of people, a genetic (hereditary) cause can be identified. Individuals with a family history of frontotemporal disorders are more likely to have a genetic form of the disease than those without such a history.

Familial and inherited forms of frontotemporal disorders are often related to mutations (permanent changes) in certain genes. Genes are basic units of heredity that tell cells how to make the proteins the body needs to function. Even small changes in a gene may produce an abnormal protein, which can lead to changes in the brain and, eventually, disease.

Scientists have discovered several different genes that, when mutated, can lead to frontotemporal disorders:

  • Tau gene (also called the MAPT gene)—A mutation in this gene causes abnormalities in a protein called tau, which forms tangles inside neurons and ultimately leads to the destruction of brain cells. Inheriting a mutation in this gene means a person will almost surely develop a frontotemporal disorder, usually bvFTD, but the exact age of onset and symptoms cannot be predicted.
  • PGRN gene—A mutation in this gene can lead to lower production of the protein progranulin, which in turn causes TDP-43, a cellular protein, to go awry in brain cells. Many frontotemporal disorders can result, though bvFTD is the most common. The PGRN gene can cause different symptoms in different family members and cause the disease to begin at different ages.
  • C9ORF72 gene—An unusual mutation in this gene appears to be the most common genetic abnormality in familial frontotemporal disorders and familial ALS. This mutation can cause a frontotemporal disorder, ALS, or both conditions in a person.
  • VCP, CHMP2B, TARDBP, and FUS genes—Mutations in these genes lead to very rare familial types of frontotemporal disorders.

Families affected by inherited and familial forms of frontotemporal disorders can help scientists further research by participating in clinical studies and trials. For more information, talk with a healthcare professional, see the resources below, search www.clinicaltrials.gov, or visit www.nia.nih.gov/health/clinical-trials.

For More Information About Causes of Frontotemporal Disorders

NIA Alzheimer’s and related Dementias Education and Referral (ADEAR) Center
1-800-438-4380 (toll-free)
adear@nia.nih.gov
www.nia.nih.gov/alzheimers
The National Institute on Aging’s ADEAR Center offers information and free print publications about Alzheimer’s disease and related dementias for families, caregivers, and health professionals. ADEAR Center staff answer telephone, email, and written requests and make referrals to local and national resources.

Association for Frontotemporal Degeneration
1-866-507-7222 (toll-free)
www.theaftd.org

National Institute of Neurological Disorders and Stroke
1-800-352-9424 (toll-free)
braininfo@ninds.nih.gov
www.ninds.nih.gov

Alzheimer's Association
1-800-272-3900 (toll-free, 24/7) 
1-866-403-3073 (TTY/toll-free)
info@alz.org
www.alz.org