Familial Alzheimer’s Disease

Less than 5% of Alzheimer’s disease (AD) is caused by a single genetic mutation that is transmitted through families. In these families, people usually show symptoms well before the age of 65 and symptoms sometimes begin as early as the 30s or 40s. This form of AD is called early-onset familial Alzheimer’s disease (EOFAD).

Three genes have been associated with EOFAD. They are:

  1. Presenilin 1 (PS1) on chromosome 14
  2. Presenilin 2 (PS2) on chromosome 1
  3. Amyloid precursor protein (APP) on chromosome 21

A mutation in any of these three genes follows an autosomal dominant inheritance pattern. 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. Clinical testing is available to detect mutations in these three genes.

Additionally, there are other variants in genes that can increase or decrease susceptibility to AD but do not cause the disease. An example is the apolipoprotein (APOE) gene.

APOE is found in three different forms: APOE 2, APOE 3 or APOE 4. Each form has different implications for AD risk. The APOE 2 form decreases risk, the APOE 3 form is neutral and the APOE 4 form increases risk. Like all other genes, each cell contains two copies of the APOE gene.

About 25 percent of the population has one copy (heterozygous) of APOE 4, and another 1 percent has two copies (homozygous). Having one copy of APOE 4 is associated with a 3-fold increased risk for AD and having two copies is associated with an 8–10 fold increased risk. It is important to emphasize that APOE 4 does not cause AD, it only increases risk. Not everybody with APOE 4 develops AD. Similarly, people without APOE 4 can still develop AD.

Other genetic, lifestyle and environmental factors also influence risk. Therefore, until preventative treatment is available, presymptomatic testing for APOE is not recommended.