Apart from longevity, family history is the principal risk factor for Alzheimer disease. It is not surprising, therefore, that those with a family history of this devastating disease are anxious to know more about its genetics.

Alzheimer's inheritedHaving a first-degree relative with Alzheimer disease approximately doubles the risk of contracting it. The review summarized here considers our present state of knowledge on this subject.

If you have a family history of Alzheimer's disease you obviously want to know more about its genetics. It's known that having a first-degree relative with Alzheimer's disease approximately doubles the risk of contracting it. A recent review has summarized our present state of knowledge. 1

Alzheimer's disease is typically divided into early-onset and late-onset forms, with 60 or 65 years of age as the dividing point. Late-onset Alzheimer's disease is far commoner than the early-onset form - the prevalence of the disease is less than 1 per 1000 for people aged 50, while it's seen in about 1 in 10 people aged 75. It may be easier to determine a family history in the early-onset form, however, as the family members usually live through the risk period. Three genes have been associated with early-onset Alzheimer's disease. Mutations of one or other of these genes have been found in relatively few patients, mostly from families with two or more affected members. The abnormal genes were found in about half the early-onset patients studied.

If a close relative has early-onset Alzheimer's, it may be possible to test family members for the presence of one or more of these genes. Gene test kits have become commercially available. Their use might help in considering management of family members with suspicious symptoms, or to assist in genetic counseling. However, it is neither practical nor sensible to offer widespread genetic screening for early-onset Alzheimer's disease at the present time.

So far only one gene for late-onset Alzheimer's disease has been identified with certainty - APOE. It occurs in a particular form ("allele") in some healthy elderly patients, but this form is more common in patients with Alzheimer's disease. Presence of the particular form seems to modify the age at onset of the disease in otherwise susceptible individuals. Its peak effect occurs in patients in their 60s, rather than in their 70s and 80s, when the disease is more common. As the presence of this gene form is not essential or sufficient on its own for Alzheimer's disease to occur, it's use is not recommended for testing if an individual is likely to develop the condition.

At a recent international conference on this subject, more than 70 reports involving at least a dozen other genes were discussed. It is clear that additional genes will be confirmed as having a role in causing Alzheimer's disease. One day, a battery of genetic targets for screening may help predict which persons might be susceptible, but this time has not yet arrived.

Other benefits from the discovery of genes associated with the occurrence of Alzheimer's disease are probably closer. The identities of the genes discovered so far already provide clues as to the early molecular changes leading to the disease. Two of them are closely involved in the production of an abnormal form of the protein amyloid; this type of amyloid is found in the microscopic brain plaques characteristic of the disease. Obviously, these findings provide enormous impetus to the search for new drugs. The discovery of additional genes associated with Alzheimer's disease will contribute still more opportunities for finding new drugs to hinder or prevent the process.

1. Footnotes

The genetics of Alzheimer disease: current status and future prospects. D Blacker, RE Tanzi, Arch Neurol, 1997, vol. 55, pp. 294--296

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