Familial Alzheimer’s disease is a rare, inherited form of Alzheimer’s that usually develops earlier than other forms of the disease. It’s due to specific genetic variants that tend to run in families.

Familial Alzheimer’s disease (FAD) is a rare, inherited form of Alzheimer’s that typically develops before the age of 65 years.

Specific gene mutations (changes) that are inherited within families cause FAD, setting it apart from the more common sporadic type of Alzheimer’s disease.

Read on to learn more about FAD, including its causes, symptoms, diagnosis, and possible treatment options.

How common is familial Alzheimer’s disease?

Familial Alzheimer’s disease is a rare form of Alzheimer’s, accounting for 15% to 25% of all cases. It results from inherited genetic mutations, which are often linked to the processing of amyloid proteins.

This condition primarily affects families with a history of early onset dementia, with symptoms usually appearing before 65 years of age.

Familial and sporadic Alzheimer’s disease have similar symptoms, but they differ in cause, inheritance, and age of onset:

  • Cause: FAD results from specific gene mutations, whereas sporadic Alzheimer’s has no single cause. Age, environment, and lifestyle typically influence the development of sporadic Alzheimer’s.
  • Inheritance: FAD follows an autosomal dominant inheritance pattern, which means a person can develop the disease by inheriting just one copy of the mutated gene from a parent. Sporadic Alzheimer’s does not follow this pattern.
  • Age of onset: FAD typically causes symptoms before 65 years of age, while sporadic Alzheimer’s usually develops after 65 years of age.

Three specific genes are known to cause FAD:

  • Presenilin 1 (PSEN1): This is the most common gene mutation in FAD, accounting for up to 5% of all cases.
  • Presenilin 2 (PSEN2): Though less commonly involved, PSEN2 mutations can also lead to FAD.
  • Amyloid precursor protein (APP): Mutations in this gene increase amyloid-beta plaque production, a key feature of Alzheimer’s disease.

These genes disrupt typical brain function, causing the buildup of amyloid plaques and tau protein tangles that damage neurons (nerve cells in the brain).

Scientists also consider these gene variants to be nearly 100% penetrant. That means that if you inherit the gene variant that’s responsible for causing FAD, you will almost certainly develop the disease.

FAD typically follows an autosomal dominant inheritance pattern. This means that having just one copy of a mutated gene from one parent is enough to significantly increase your risk of developing the disease.

If a parent has a mutation in the APP, PSEN1, or PSEN2 gene, each child has a 50% chance of inheriting that mutation and possibly developing FAD, often at a younger age than in typical Alzheimer’s cases.

Genetic testing can identify these mutations. But consider talking with a genetic counselor before testing, as the results may affect your emotions and decision making.

How likely am I to have Alzheimer’s disease if my parents had it?

If you have a parent with Alzheimer’s disease, you may have an increased risk of developing the disease yourself. Although a single genetic cause does not determine Alzheimer’s, certain gene variants can affect your risk.

If one of your parents has familial Alzheimer’s disease (FAD), there is a 50% chance that you inherited the genetic mutation. But not all cases of Alzheimer’s in families are due to FAD. A genetic counselor can help determine whether your family’s history fits the FAD pattern.

For sporadic Alzheimer’s, having a first-degree relative, such as a parent or sibling, who has the disease increases your risk by 10% to 30%, especially if they developed it at an early age.

People with FAD often experience symptoms similar to those of late onset Alzheimer’s disease, such as:

  • memory loss
  • confusion about place or time
  • difficulty planning or solving problems
  • changes in personality or mood

Some people with familial Alzheimer’s genetic mutations may also experience seizures, changes in gait, or spastic paraparesis (a form of muscle weakness affecting the legs), though these symptoms are less common.

To diagnose FAD, doctors start with a detailed medical history to identify patterns of early onset Alzheimer’s in the family. They may ask about the age at which symptoms began and whether other family members had similar experiences.

Next, they’ll perform a physical exam and cognitive tests. These tests evaluate memory, problem-solving, and other cognitive functions to detect early signs of Alzheimer’s. Symptoms appearing in younger people may indicate FAD.

A doctor may order imaging studies, such as an MRI or a PET scan. These scans can reveal brain changes such as tissue shrinkage (atrophy) and amyloid plaque buildup, which are features of Alzheimer’s disease.

To confirm the diagnosis, a doctor may recommend genetic testing. This involves testing for mutations in the APP, PSEN1, and PSEN2 genes, which are often linked with FAD. Genetic testing is useful for families with a history of early onset Alzheimer’s to confirm the disease.

There is currently no treatment available that can cure FAD or prevent its progression.

However, doctors may use medications that are approved for treating some stages of Alzheimer’s to manage symptoms in people with FAD.

Possible treatment strategies may include:

  • Medications: Cholinesterase inhibitors, such as donepezil (Aricept), and NMDA receptor antagonists, such as memantine (Namenda), may help manage symptoms.
  • Lifestyle interventions: Regular exercise, mental stimulation, and a nutritious diet may help slow the progression of the disease.
  • Clinical trials: Families with FAD may qualify for research studies testing new therapies, which may offer access to potential treatments.

FAD typically progresses more quickly because of its genetic nature. Symptoms often start earlier, usually between a person’s 30s and 60s, and gradually progress over time.

Although treatments can help manage the symptoms, there is no cure, so supportive care is essential. Life expectancy varies depending on the disease’s progression rate, but most people live about 8 to 10 years after symptoms begin.

FAD may contribute to various advancements in Alzheimer’s research, including:

  • Providing genetic clarity: Understanding APP, PSEN1, and PSEN2 mutations helps researchers identify how the disease develops and progresses.
  • Developing new therapies: Clinical trials in FAD populations provide important data for developing treatments that could work for all types of Alzheimer’s.
  • Advancing diagnosis and prevention: FAD research supports the development of early diagnostic tools and prevention strategies, as symptoms often follow predictable patterns in affected families.

Can genetic testing determine if someone will develop familial Alzheimer’s disease?

Yes, genetic testing can detect mutations in the APP, PSEN1, and PSEN2 genes. Having a mutation in one of these genes means you will almost certainly develop FAD. Genetic counseling is essential to discuss potential outcomes and provide support.

However, genetic testing is not reliable in detecting sporadic forms of Alzheimer’s.

How does familial Alzheimer’s disease affect family planning decisions?

Options such as preimplantation genetic testing during IVF can help reduce the risk of passing on FAD-associated mutations. Genetic counseling can guide these decisions.

What support is available for families affected by familial Alzheimer’s disease?

Support groups, online communities, and organizations like the Alzheimer’s Association provide resources, emotional support, and guidance for affected families.

FAD is a rare, inherited form of Alzheimer’s that typically develops in people ages 30 to 65 years.

The symptoms of FAD are similar to those of sporadic Alzheimer’s but appear earlier and progress more quickly. Genetic testing and counseling can confirm the condition and support family planning decisions.

While there’s no cure for FAD, medications and lifestyle changes can help manage the symptoms, and participation in clinical trials may provide access to experimental treatments.