Familial Alzheimer’s Disease

Familial Alzheimer’s Disease (FAD) is a very rare form of Alzheimers, and runs in very few families. If a parent has a specific mutated gene, then any children have a 50% chance of inheriting and developing the disease. The presence of the specific mutated gene means that the person will eventually develop Alzheimers disease, usually in their 40s or 50s.

This form of Alzheimers affects a very small number of people. The total known number of FAD cases worldwide is about 200 people. All instances of FAD that have been studied so far have a much earlier onset, and as many as 50 percent of FAD cases are now known to be caused by defects in one or more of three genes located on three different chromosomes inside the person’s cells:

1.Amyloid Precursor Protein (APP) Mutation: Some families have mutations in a gene called amyloid precursor protein (APP), which causes an abnormal form of the amyloid protein to be produced.

2.Presenilin 1 Mutation: Other families have mutations in a gene called presenilin 1, which causes an abnormal presenilin 1 protein to be produced.

3.Presenilin 2 Mutation: Presenilin 2 is a gene very similar to presenilin 1, and when this gene is mutated, then it causes an abnormal presenilin 2 protein to be produced.

Any of these mutations are believed to cause FAD. Furthermore, even if only one of these mutations is present, and it is present in only one of the two matching genes inherited from their parents, then the person will still inevitably develop FAD.

This type of genetic inheritance is known as autosomal dominant inheritance. There is no evidence at this stage that any of these mutations play a major role in the far more common sporadic (i.e. late-onset) Alzheimer’s.

Scientists are striving to reveal the normal function of Amyloid Precursor Protein (APP) and the presenilin proteins to determine how mutations of these genes cause the onset of FAD.