Introduction to familial Alzheimer's disease
Familial Alzheimer’s disease (FAD), also known as Autosomal Dominant Alzheimer’s Disease (ADAD), is a rare form of Alzheimer’s disease caused by specific genetic mutations that run within families. Familial Alzheimer’s disease probably accounts for less than 1% of cases of Alzheimer’s disease overall and generally affects people at a younger age than the more common sporadic (non-inherited) form of Alzheimer’s disease. The age at which people develop symptoms varies considerably between different families but is typically before the age of 65. In some families, individuals may be as young as their early 30’s when they become affected. Within a single family, people tend to develop the disease at broadly similar ages.
Familial Alzheimer’s disease is caused by a fault (mutation) within a gene. Three genes have been found to contain mutations that lead to the disease. These are called the presenilin 1 and presenilin 2 (PSEN1 and PSEN2) and amyloid precursor protein (APP) genes. Many different mutations have been identified in each of these genes and more continue to be discovered. It has also been found that possessing an extra copy of the APP gene (an APP duplication) can give rise to familial Alzheimer’s disease. All three of these genes are involved in how amyloid, a protein found in the brain, is deposited in brain tissue. These mutations run in families and show a pattern of inheritance that is described as ‘autosomal dominant’.
This means that in each family the disease is caused by a mutation in a single gene and that a single copy of the mutant gene, inherited from one parent, will cause the disease.
In autosomal dominantly inherited diseases like familial Alzheimer’s disease, the risk of a parent passing a mutation on to their children is 50% (1 in 2 chance) for each pregnancy. An affected parent could have all children affected, or all children unaffected, or a mixture. The disease affects males and females equally and does not skip generations. However, it may appear to skip a generation if a person with the faulty gene dies of another cause before the illness develops. As far as we know, individuals who inherit the faulty gene will go on to develop the disease if they live long enough.
Individuals with familial Alzheimer’s disease usually have a strong family history of the illness, which means that they know of cousins, aunts/uncles and grandparents who were affected at a similar age, as well as one of their parents. In some cases an individual may not know whether they have a family history of Alzheimer’s disease, for example if they do not know their biological parents or if their parents died young. When it is unknown in this way, the family history is said to be ‘censored’.
Whilst familial Alzheimer’s disease mutations are rare and typically cause symptoms at a young age, Alzheimer’s disease as a whole is such a common condition, particularly in the elderly, that many people have a relative with Alzheimer’s disease. Although certain risk genes may play a role in the development of late-onset Alzheimer’s disease, many other factors also contribute and possession of a risk gene does not mean that an individual will necessarily develop Alzheimer’s disease. This is a very different situation to what occurs in familial Alzheimer’s disease, where the disease is entirely caused by inheriting a faulty gene.
If someone has a relative with Alzheimer’s disease and is concerned about whether it may be familial, they should gather as much information as they can about their relative’s family history so that they can discuss it with the doctor caring for their relative. Useful information would include how old family members were when they died, whether they had dementia and, if so, the age at which they developed symptoms.