Primary progressive aphasia (PPA) affects a person's ability to use language to communicate. This includes difficulty making or understanding speech (aphasia). PPA is a specific type of a more general disease called frontotemporal dementia. PPA can be classified into three distinct types which include:

• Progressive non-fluent aphasia (PNFA)
• Semantic dementia (SD)
• Logopenic progressive aphasia (LPA)

PPA is caused by a loss of tissue (atrophy) in the area of the brain that is responsible for producing language. In some cases, this loss of tissue is caused by genetic changes (mutations or pathogenic variants) in the GRN gene. In these cases, the disease is inherited in an autosomal dominant manner. Diagnosis of PPA is suspected when a doctor observes signs and symptoms such as progressive loss of language abilities. Imaging of the brain with a CT scan or MRI can confirm the diagnosis. Although there is no cure for the disease, treatment options include speech therapy and medication to manage behavioral changes.

About 40-50% of people with primary progressive aphasia (PPA) have other family members who are also affected by the disease. When PPA is caused by a genetic change (mutations or pathogenic variants) in the GRN gene, it is inherited in an autosomal dominant manner. Like most genes, the GRN gene comes in a pair. One copy of the gene comes from the mother and the other copy from the father. Autosomal dominant means that only one copy of the GRN gene needs to have a pathogenic variant for a person to develop PPA.

When a person who has a pathogenic variant in the GRN gene has children, each child has a:

• 50% chance to inherit the changed copy of the GRN gene, meaning he or she is at an increased risk to develop PPA
• 50% chance to inherit the working copy of the GRN gene, meaning he or she is not at an increased risk to develop PPA

Most cases of PPA are not caused by a pathogenic variants in the GRN gene, but PPA can still run in families. In these situations, the disease is likely more common in the family because of shared genetic and environmental factors.