THE DEMENTIA GENES

Alzheimer’s genes: Are you at risk?

Researchers have identified a number of genes associated with Alzheimer’s disease. Some genes increase your likelihood of developing the disease (risk genes). Others guarantee that you will develop a disease (deterministic genes) are rare. However, genetic risk factors are just one of the factors involved in getting Alzheimer’s disease.

Most common late-onset Alzheimer’s gene

The most common type of Alzheimer’s disease usually begins after age 65 (late-onset Alzheimer’s disease). The most common gene associated with late-onset Alzheimer’s disease is a risk gene called apolipoprotein E (APOE).

APOE has three common forms:

• APOE e2 — the least common — reduces the risk of Alzheimer’s.
• APOE e4 — a little more common — increases the risk of Alzheimer’s and is associated with getting the disease at an earlier age. Approximately 15% to 25% of the general population carries an APOE e4 allele.
• APOE e3 — the most common — doesn’t seem to affect the risk of Alzheimer’s

family history matters

Because you inherit one APOE gene from your mother and another from your father, you have two copies of the APOE gene. Having at least one APOE e4 gene increases your risk of developing Alzheimer’s disease two- to threefold. If you have two APOE e4 genes, your risk is even higher, approximately eight- to twelvefold.

But not everyone who has one or even two APOE e4 genes develops Alzheimer’s disease. And the disease occurs in many people who don’t even have an APOE e4 gene, suggesting that the APOE e4 gene affects risk but is not a cause. Therefore even with the genetic risk improving the other risk factors could signficantly reduce the risk

As with APOE, these genes are risk factors, not direct causes. In other words, having a variation of one of these genes may increase your risk of Alzheimer’s. However, not everyone who has one will develop Alzheimer’s disease.

Young-onset Alzheimer’s

A very small percentage of people who develop Alzheimer’s disease have the young-onset type. Signs and symptoms of this type usually appear between ages 30 and 60 years. This type of Alzheimer’s disease is very strongly linked to your genes.

Scientists have identified three genes in which mutations cause early-onset Alzheimer’s disease. However there are probably more.to be discovered. If a person inherit one of these mutated genes from either parent, they will probably have Alzheimer’s symptoms before age 65. The genes involved are:

• Amyloid precursor protein (APP)
• Presenilin 1 (PSEN1)
• Presenilin 2 (PSEN2)

Mutations of these genes cause the production of excessive amounts of a toxic protein fragment called amyloid-beta peptide. This peptide can build up in the brain to form clumps called amyloid plaques, which are characteristic of Alzheimer’s disease. 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.

As amyloid plaques collect in the brain and eventually stick together to form neurofibrillary tangles. These tangles are associated with the abnormal brain functions seen in Alzheimer’s disease.

Genetic testing

Most experts don’t recommend genetic testing for late-onset Alzheimer’s. In some instances of early-onset Alzheimer’s, however, genetic testing may be appropriate.

Most clinicians discourage testing for the APOE genotype because the results are difficult to interpret. And doctors can generally diagnose Alzheimer’s disease without the use of genetic testing.

Testing for the mutant genes that have been linked to early-onset Alzheimer’s may provide more-certain results if you’re showing early symptoms or if you have a family history of early-onset disease. Genetic testing for early-onset Alzheimer’s may also have implications for current and future therapeutic drug trials as well as for family planning.Before being tested, it’s important to weigh the emotional consequences of having that information and your eligibility for certain forms of insurance, such as disability, long-term care and life insurance.