Genes and Alzheimer Disease

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The summary below is from the full report titled "Apolipoprotein E 4 Allele, Elevated Midlife Total Cholesterol Level, and High Midlife Systolic Blood Pressure Are Independent Risk Factors for Late-Life Alzheimer Disease." It is in the 6 August 2002 issue of Annals of Internal Medicine (volume 137, pages 149-155). The authors are M Kivipelto, E-L Helkala, MP Laakso, T Hänninen, M Hallikainen, K Alhainen, S Iivonen, A Mannermaa, J Tuomilehto, A Nissinen, and H Soininen.

What is the problem and what is known about it so far?

There are thousands of genes in a human body cell. The genes occur on 23 pairs of chromosomes. Each gene on a chromosome has a counterpart on the matching chromosome. Genes in a matching pair may be identical or different. Different forms of the same gene are known as alleles. A single gene may have a few or several hundred different alleles. Alleles account for the inherited differences among people, such as varying eye and hair color. Alleles may also play a part in the cause and progression of diseases.

Alzheimer disease is characterized by progressive loss of mental abilities (dementia). It is the most common type of dementia. It usually occurs after 60 years of age. The exact cause of Alzheimer disease is not known. Several factors probably play a role, including a specific allele of a gene called apolipoprotein E (apoE 4 allele), high blood pressure, and high cholesterol level. However, how these factors relate to each other in increasing the risk for Alzheimer disease has not been clear.

Why did the researchers do this particular study?

To see whether having the apoE 4 allele increases a person's risk for Alzheimer dementia, independent of blood pressure and cholesterol level.

Who was studied?

1449 Finnish adults 65 to 79 years of age.

How was the study done?

The researchers started this study in the 1970s and 1980s. During that time, the researchers invited random samples of people living in two towns in Finland to answer several questions about their health. Participants also had their blood pressure measured and blood samples taken. During 1997 and 1998, the researchers asked 2000 of the original participants to return for another evaluation. Of these 2000 people, 1449 returned to answer several follow-up questions about their health, including questions that assessed whether they had dementia. The researchers then looked at whether apoE 4 and blood pressure and cholesterol levels measured during examinations from the initial studies were related to having dementia later in life.

What did the researchers find?

The apoE 4 allele, high cholesterol levels, and high systolic blood pressure all independently increased the risk for Alzheimer disease. The degree of risk associated with high systolic blood pressure and high cholesterol levels appeared greater than the risk associated with the apoE 4 allele.

What were the limitations of the study?

The study could look only at whether certain factors are associated with an increased risk for dementia. The study does not tell us whether treating high blood pressure and high cholesterol will reduce risk. In addition, some people who participated in the original examinations (from 1970 to 1980) died before the 1997 to 1998 reexamination period. Some of these patients may have had dementia, and factors associated with their dementia may have been different.

What are the implications of the study?

Having the apoE 4 allele, a high cholesterol level, or high systolic blood pressure increases a person's risk for dementia in later life. Although this study did not test benefits of treatment, factors that are potentially treatable (high cholesterol level and blood pressure) may be more important than "what is in the genes" (the apoE 4 allele).