Alzheimer's disease: can it be inherited?
About a third of people with Alzheimer’s disease have a close relative (parent, brother or sister) who has, or has had, dementia. The other two thirds of people with Alzheimer’s disease probably do not have any family history. In these cases, the disease is known as ‘sporadic’.
Alzheimer’s disease occurs relatively frequently in the elderly, regardless of a family history. When a person does not have a first degree relative (parent, brother or sister) with a history of Alzheimer’s disease, the risk of getting Alzheimer’s disease is related to the person’s current age; for example, a one in 100 chance between 60 and 64 years, a one in 20 between 70 and 74 years and a more than one in 5 chance after age 80 years.
This means if you trace your family tree and find 20 relatives who lived to 65, it is likely one will have had dementia by chance. If you find five who lived to 85, it is likely one will have had dementia. In both cases, this can be by chance and not evidence of inheritance. At the present time, it is thought that this implies just bad luck rather than ‘bad genes’.
What are the risk factors?
Risk factors to the development of Alzheimer’s disease include exposures to a substance or product, family background or work history. Just as, for example, if an individual smokes, he or she is more likely to develop lung cancer than someone who doesn’t smoke.
Risk factors may not be causes in themselves, they may simply make a person more susceptible to developing a certain disease, if other factors are present. For example, fair skinned people who are sun exposed can get skin cancer. Without the sun exposure, fair skin does not lead to skin cancer.
Family history as a risk factor
Family history is only one risk factor for Alzheimer’s disease. In most cases of Alzheimer’s disease no risk factors can be identified. You are not necessarily at increased risk of developing Alzheimer’s disease if:
- you only had a grandparent who had Alzheimer’s disease;
- your parent got Alzheimer’s disease over the age of 65; or
- your parent had the onset of Alzheimer’s disease before the age of 65, and you are now several years older than that.
It is also important to note that:
- when considering inheritance risks, only biologically related relatives should be included. Do not count a relative on your mother's side and one on your father's side as being from the same family tree! Do not include half or step relatives (or non-blood relatives or adopted relatives).
You may be at increased risk of inheriting Alzheimer’s disease if you have a parent, brother or sister with Alzheimer’s disease. However this risk is difficult to prove, unless there are other blood relatives affected as well. Therefore, you may have an increased risk if both of the following apply to you:
- Family incidence
Two generations or more of first degree relatives (parent and brother or sister or grandparent and parent on the same side of the family had Alzheimer's disease (and not any other form of dementia). Age of onset
The onset of the disease was before 65 years of age in both relatives.
A family history of Alzheimer’s disease
The disease known as familial Alzheimer’s disease or FAD is a form of Alzheimer’s disease known to be entirely inherited (see below for a description of types of early onset FAD). In these families, members of at least two generations can be documented to have Alzheimer’s disease. Although about one third of people with Alzheimer’s disease have an affected relative, fewer than one in 100 are likely to have familial Alzheimer’s disease.
Understanding genetics
Everyone has an intuitive understanding of heredity. Each of us know that some characteristics run in our family: blue eyes, big noses, curly hair and so on. Human genetics is the scientific study of heredity. Following are some basics which you’ll need to understand genetics in Alzheimer’s disease.
DNA
We resemble our parents because we inherit genetic material from them. This genetic material which is a complex chemical called DNA, is packaged into structures called chromosomes. The DNA acts as a blueprint for us: it determines how we look and, to a certain extent, to which diseases we will be susceptible.
Chromosomes
We have 22 pairs of chromosomes plus two X chromosomes (women) or an X and Y chromosome (men). The 22 chromosomes are numbered 1-22 in decreasing order of size. We inherit one of each pair of chromosomes from our mother (in her egg) and one of each pair from our father (in his sperm). They inherited one from each of their parents (our grandparents). It is because all the children in a family inherit a different combination of the DNA from their parents that they look similar but not the same (except in the special case of identical twins who arise from the same egg and sperm).
Genes
Each chromosome contains thousands of genes, like beads on a string. Unlike the chromosomes, we cannot see the genes even under a microscope. The genes are the basic units of heredity that allow specific attributes or characteristics to be passed from one generation to the next. For each characteristic, we inherit two genes (one from mother and one from father) which are found one on each of the chromosome pairs 1-22 and the XX or XY pair. Both genes may be expressed in creating a specific attribute or characteristic. Sometimes only one gene from a pair is expressed. This is called: the ‘dominant’ gene; the other one, called ‘recessive’, is silent.
Recessive genes only become apparent (e.g. blue eyes, Tay-Sachs disease) if they are not ‘overpowered’ by a dominant gene because the person has inherited a pair of recessive genes from both mother and father. For other attributes or characteristics, both chromosomes play a role: such genes are neither dominant nor recessive.
Mutations
A mutation is change in a gene. Once a mutation occurs it is permanent and can be passed on from generation to generation. Some mutations alter specific attributes or characteristics and can result in a disease or a disease susceptibility. Other mutations are recessive or silent: they are not evident in an individual but can still be transmitted to the next generation.
Genetics in Alzheimer’s disease
There are two different types of genetic influences on Alzheimer’s disease. The first group is the early onset (before the age of 65 years) FAD group. It contains mutations which are mainly dominant. The second group are the late onset (generally aged 65 years or older) forms of Alzheimer’s disease. These are not necessarily familial and do not have mutations. However, this second group may have variants of normal genes which increase a person's susceptibility or risk of developing Alzheimer’s disease.
Causes of early onset familial Alzheimer's disease (FAD)
To date, scientists have identified mutations (changes) of genes on three chromosomes (1, 14 and 21) known as causing early onset FAD. It is important to note that these mutations and early onset FAD persons are very rare. For example, only 10-15 families worldwide have been reported with mutations on the APP gene on chromosome 21. On chromosome 1, the mutation has only been found in families belonging to a particular family group called the Volga Germans (none so far have been found in Australia). Several mutations of the gene on chromosome 14 that have been identified are also rare, but they account for 80 per cent of early onset FAD cases.
What is the risk of inheriting Alzheimer's disease if my family has early onset FAD?
Because we inherit half our genes from each parent, each child of an affected parent in these families has a 1 in 2 (50 per cent) chance of developing Alzheimer’s disease. For each of our genes there is an equal chance that we have inherited it from our mother or our father. This means that on average, half of the children of an affected parent will develop the disease, but half will not. This is referred to as ‘autosomal dominant’ inheritance.
People sometimes ask whether they are more at risk than their brothers or sisters because they share some physical or temperamental characteristic with the affected parent. The answer is no. It does not mean they are at increased risk of the disease as genes are mostly inherited in a random fashion. Thus physical or emotional similarity to an affected person does not increase the chance of inheriting the Alzheimer’s disease gene.
If there are two or more first degree relatives in your family who have had early onset Alzheimer's disease
If you are concerned about your own or a family member’s risk of inheriting Alzheimer’s disease, you may ring the Alzheimer’s Association NSW Helpline, 1800 639 331. It is recommended that you ensure it is Alzheimer's disease.
It is essential to ensure that suspected cases in your family really have (or had) Alzheimer’s disease and not another form of dementia. This can only be done through medical assessment if the relative is still alive. Diagnosis of Alzheimer’s disease after formal specialist assessment is correct about 85 per cent of the time without an autopsy.
If your relative is no longer living, confirmation that the person had Alzheimer’s disease may be able to be determined through a careful review of autopsy reports and medical records, if available. It is also helpful to prepare a family tree of your genetic history. The Alzheimer’s Association NSW has a supply of such forms which have been produced by the NSW Genetic Education Program.
Have blood tests
In cases where the affected person is still alive and there is strong evidence of familial Alzheimer's disease (that is, where a person with the disease coming on before the age of 65 is the offspring of a parent who also had it before the age of 65), blood from the living affected family member can be tested for known mutations on chromosome 1, 14 and 21. If a treatment became available and was specific for people with these mutations, this information would be of great importance.
If a mutation is found in a family, predictive testing would be possible. People in such families have to think carefully whether they want to have such a test. Informed consent is required for a test and no one should be forced to have such a test. The results can only be given in confidence, directly to the person who had the test. To help people in coming to a decision, specialised genetic counselling is essential.
Last Reviewed: 09 October 2001
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