Researchers do not know the exact cause of Alzheimer's disease, but it likely is due to a variety of genetic and environmental factors. Genetic research is concentrating on the role of heredity — the transmission of qualities from parents to children — in the risk for and development of Alzheimer’s disease.
How does heredity work?
Every healthy person has 46 chromosomes in 23 pairs. Usually, people receive one chromosome in each pair from each parent. Chromosomes are rod-like structures in the cell nucleus. In each chromosome, DNA forms two long, intertwined, thread-like strands that carry inherited information in the form of genes.
Genes are the basic units of heredity that can direct almost every aspect of the construction, operation, and repair of living organisms. Each gene is a set of chemical instructions that tells a cell how to make one of the many unique proteins in the body. Every human cell has from 50,000 to 100,000 genes arranged on the chromosomes like beads on a string.
Genes are made up of four chemicals (bases) arranged in various patterns along the strands of DNA. In each gene, the bases are lined up in a different order, and each sequence of bases directs the production of a different protein. Even slight changes in a gene's DNA code can make a faulty protein, and a faulty protein can lead to cell malfunction and possibly disease.
Is Alzheimer’s disease hereditary?
Genetic research has turned up evidence of a link between Alzheimer's disease and genes on four chromosomes, 1, 14, 19, and 21. The apoE4 gene on chromosome 19 has been linked to late-onset Alzheimer's disease, which is the most common form of the disease.
Researchers also are looking for proteins that bind to beta amyloid. One version of a protein called apolipoproteinE (apoE) does bind quickly and tightly to beta amyloid, but apolipoproteinE is well known as a carrier of cholesterol in blood.
The gene apoE, which produces the protein, also is on chromosome 19. Moreover, it is on the same region of chromosome 19 as the Alzheimer's gene for which they had been searching. Scientists decided to see if the apoE gene and the still missing Alzheimer's gene could be one and the same: They found the apoE gene was identical to the gene they had been seeking. ApoE, it turned out, is much more common among Alzheimer's patients than among the general population. Since that finding, dozens of studies around the world have confirmed that the apoE gene increases the risk of developing Alzheimer's disease.
The theories surrounding apoE are not confined to the proteins. One finding that intrigues neuroscientists is that Alzheimer's patients with the apoE gene have neurons with shorter dendrites, the branchlike extensions that receive messages from other neurons. Researchers speculate that the dendrites have been pruned back by some unknown agent, limiting the neuron's ability to communicate with other neurons. Although this pruning can also occur in people without the apoE gene, it happens 20 or 30 years earlier in people with apoE.
One of the puzzles surrounding apoE is why some people with the gene do not develop Alzheimer's disease and why, conversely, many people develop the disease even though they do not have the gene. ApoE, in other words, is not a consistent marker for Alzheimer's.
What is the role of genetics in familial Alzheimer’s disease (FAD)?
Alzheimer's disease strikes early and fairly often in certain families, often enough to be singled out as a separate form of the disease and given a label: early-onset familial Alzheimer's disease or FAD. Combing through the DNA of these early-onset families, researchers have found a mutation in one gene on chromosome 21 that is common to a few of the families. They have also linked a larger proportion of early-onset families to recently identified genes on chromosomes 1 and 14.
The chromosome 21 gene carries the code for a mutated form of the amyloid precursor protein, APP, the parent protein for beta amyloid. The discovery of this gene supports the theory that beta amyloid plays a role in Alzheimer's disease, although the mutation occurs in only about 5 percent of early-onset families.
The chromosome 21 gene intrigues Alzheimer's researchers also because it is the gene involved in Down syndrome. People with Down syndrome have an extra version of chromosome 21 and, as they grow older, usually develop plaques and tangles like those found in Alzheimer's disease.
Few researchers think that the search for Alzheimer's genes is over. Most investigators are convinced that there are several genes involved in Alzheimer's disease and, moreover, that other conditions must also be present for the disease to develop. One of these conditions might be a problem with the way in which neurons turn sugar, or glucose, into energy, a process known as glucose metabolism .
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This information is provided by the Cleveland Clinic and is not intended to replace the medical advice of your doctor or health care provider. Please consult your health care provider for advice about a specific medical condition. This document was last reviewed on: 5/28/2003
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