Early Onset Familial Alzheimer’s Disease

Early onset familial Alzheimer’s disease is a rare inherited form of dementia that strikes people before age 65, sometimes as early as their 30s or 40s, caused by specific genetic mutations passed down through families.

Table of contents

• What is Early Onset Familial Alzheimer’s Disease?
• How Common is This Condition?
• Genetic Causes and Inheritance
• Signs and Symptoms
• Getting a Diagnosis
• How the Disease Progresses

What is Early Onset Familial Alzheimer’s Disease?

Early onset familial Alzheimer’s disease, often called EOFAD, is a form of Alzheimer’s disease that occurs when symptoms begin before age 65.^[1] Unlike the more common form of Alzheimer’s that develops in older adults, this condition is caused by a single genetic mutation that runs in families.^[1]

People with EOFAD usually show symptoms well before the age of 65, and symptoms sometimes begin as early as the 30s or 40s.^[1] Many people with early-onset disease are in their 40s and 50s when the condition strikes.^[4] This timing means the disease often affects people while they are still working, raising families, or serving as caregivers themselves.^[4]

How Common is This Condition?

EOFAD is very rare. Less than 5% of all Alzheimer’s disease cases are caused by a single genetic mutation that is transmitted through families.^[1] Among all people with Alzheimer’s disease, only about 5 to 10% have the early-onset form that begins before age 65.^[2]

Of those with early-onset Alzheimer’s, only about 10 to 15% have the familial form caused by genetic mutations.^[2] This means that most cases of early-onset Alzheimer’s are not directly caused by known genetic mutations and are referred to as “sporadic.”^[2] Only a few hundred people have the genes that cause familial Alzheimer’s disease.^[12]

Genetic Causes and Inheritance

Three Genes Linked to EOFAD

Three genes have been associated with early onset familial Alzheimer’s disease.^[1] They are:

• Presenilin 1 (PS1 or PSEN1) on chromosome 14
• Presenilin 2 (PS2 or PSEN2) on chromosome 1
• Amyloid precursor protein (APP) on chromosome 21

The most common mutation that causes familial Alzheimer’s disease is in the PSEN1 gene.^[12] To date, 230 mutations in presenilin and amyloid precursor protein genes have been identified in EOFAD.^[3]

How the Mutations Are Passed Down

A mutation in any of these three genes follows an autosomal dominant inheritance pattern.^[1] This means that if a parent has a mutation in one of the EOFAD genes, each child has a 50% (1 in 2) chance to inherit the same mutation.^[1]

It only takes one copy of the gene mutation to cause familial Alzheimer’s disease.^[12] A person who inherits at least one copy of a mutated gene will likely develop Alzheimer’s disease before age 65.^[5] The disease does not skip generations.^[12] If one of your parents has familial Alzheimer’s disease, your cousins, aunts, uncles, or grandparents who are on that parent’s side of your family may also have it.^[12]

How the Mutations Cause Disease

The mutations within these three genes affect a common pathway in how the body produces and breaks down amyloid precursor protein.^[3] When any of these genes is altered, large amounts of a toxic protein fragment called amyloid beta peptide are produced in the brain.^[6]

This peptide can build up in the brain to form clumps called amyloid plaques, which are characteristic of Alzheimer’s disease.^[6] A buildup of toxic amyloid beta peptide and amyloid plaques may lead to the death of nerve cells and the progressive signs and symptoms of this disorder.^[6]

Genetic Testing

Clinical testing is available to detect mutations in these three genes.^[1] Individuals with a family history of early-onset Alzheimer’s should consider genetic counseling to assess their risk and discuss potential preventive measures.^[5]

Signs and Symptoms

Early-onset familial Alzheimer’s disease shares the same symptoms as typical Alzheimer’s disease. The main difference is when symptoms first appear.^[8]

Memory Problems

Memory loss is the most common sign of Alzheimer’s disease.^[6] Forgetfulness may be subtle at first, but the loss of memory worsens over time until it interferes with most aspects of daily living.^[6] Early signs include unusual memory loss, particularly in remembering recent events and the names of people and things.^[2]

Even in familiar settings, a person with Alzheimer’s disease may get lost or become confused.^[6] Routine tasks such as preparing meals, doing laundry, and performing other household chores can be challenging.^[6]

Thinking and Reasoning Difficulties

As the disease progresses, people exhibit more serious problems with thinking and reasoning. They may have difficulty with problem-solving and decision-making.^[2] It may become difficult to recognize people and name objects.^[6]

Language and Communication Changes

Problems with speaking or writing may develop.^[2] People may have trouble with visual images and spatial relationships, which can affect their ability to navigate their environment.^[2]

Behavior and Personality Changes

Some people with Alzheimer’s disease experience personality and behavioral changes and have trouble interacting in a socially appropriate manner.^[6] Common symptoms include agitation, restlessness, withdrawal, and loss of language skills.^[6]

Other symptoms may include mood swings, poor judgment, confusion, decreased or poor judgment, withdrawal from work or social activities, and changes in mood and personality.^[2]

Advanced Symptoms

Affected people increasingly require help with dressing, eating, and personal care.^[6] Other symptoms in later stages may include hallucinations, seizures, decreased muscle tone, urinary and fecal incontinence, and mutism.^[2] People with Alzheimer’s disease usually require total care during the advanced stages of the disease.^[6]

Getting a Diagnosis

Getting an accurate diagnosis of early-onset Alzheimer’s can be a long and frustrating process.^[4] Since health care providers generally don’t look for Alzheimer’s disease in younger people, symptoms may be incorrectly attributed to stress or there may be conflicting diagnoses from different health care professionals.^[4]

If you are experiencing memory problems, you should have a comprehensive medical evaluation with a doctor who specializes in Alzheimer’s disease.^[4] Getting a diagnosis involves a medical exam and possibly cognitive tests, a neurological exam (a test to check how your nervous system is working) and brain imaging.^[4]

How the Disease Progresses

Individuals with Alzheimer’s disease usually survive 8 to 10 years after the appearance of symptoms, but the course of the disease can range from 1 to 25 years.^[6] Survival is usually shorter in individuals diagnosed after age 80 than in those diagnosed at a younger age.^[6]

In Alzheimer’s disease, death usually results from pneumonia, malnutrition, or general body wasting.^[6]