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What do we know about Alzheimer's disease?

Several changes occur in the brains of people with Alzheimer's disease. The brain cells shrink or disappear, and are replaced by dense, irregularly-shaped spots, or plaques. Another indicator of Alzheimer's disease is threadlike tangles around existing brain cells. These tangles eventually choke healthy brain cells.

Beta Amyloid Protein

Since Alzheimer's disease was first discovered in 1906, scientists have been studying plaques and tangles to find out what causes the injury or damage to brain cells. Research has discovered that plaques, for example, contain a protein called beta amyloid. The beta amyloid found in the plaques is part of a larger substance called beta amyloid precursor protein. This precursor protein is present in all nerve cells and its specific function is unknown. In the brains of people with Alzheimer's disease, the beta amyloid splits from the larger protein. Why and how this occurs continues to be studied.

TAU Protein

Research has also discovered that tangles contain a protein called tau. Tau proteins are present in normal brains. However, in the brains of people with Alzheimer's disease, the tau proteins appear to be abnormal. Why and how this abnormal form of the tau protein occurs are areas being studied by scientists.

What do we know about genetics?

Genetics is the study of how human characteristics are passed from one generation to the next.
To better understand the relationship between Alzheimer's disease and genetics, it is helpful to know some terms.

Chromosomes:: Each individual has 46 chromosomes (rod-like structures found in every cell of the body) in 23 pairs. Each person receives one chromosome in the pair from the mother and the other chromosome from the father.
Genes:: Each chromosome carries many genes that are strung together like beads on a string. These genes are the basic units that allow specific characteristics to be passed from one generation to the next.
Alleles:: Alleles are copies of a gene. A person inherits two alleles of a gene, one from the mother and one from the father.
Dominant and recessive:: The effect of various alleles of a given gene can be dominant or recessive. Some alleles are stronger and can affect characteristics on their own; these would be dominant. Other alleles have a weaker affect and require two copies of the allele to affect a characteristic; these would be recessive.
Mutations:: Mutations are genes that have undergone a change. Once a mutation occurs, it can be passed from one generation to the next. A mutation can cause a disease, make a person more susceptible to developing a disease, or have no visible effect.

What do we know about Alzheimer's disease and heredity?

Many studies indicate that people with a relative (parent, brother or sister) with Alzheimer's disease have a greater chance of developing the disease than those with no family history.

The more common form of Alzheimer's disease is called Sporadic Alzheimer's Disease and accounts for 90 to 95 per cent of all cases. The role of heredity in Sporadic Alzheimer's Disease is unclear and continues to be the subject of intense research.

A rare form of the disease, Familial Autosomal Dominant Alzheimer's Disease (FAD), accounts for approximately five to 10 per cent of all cases. It is known to be inherited -- the disease will occur if the disease gene is present. In certain families, FAD is passed directly from one generation to another through a dominant inheritance pattern. This means that if a parent is affected, each child has a 50 per cent chance of inheriting the disease gene and will develop Alzheimer's disease in adulthood.

What do we know about certain chromosomes and Alzheimer's disease?

Genetic research has identified a relationship between Alzheimer's disease and several chromosomes:

Chromosome 1, autosomal dominant, with age of onset between 40 to 85 years.
Chromosome 14, autosomal dominant, with age of onset between 28 to 65 years.
Chromosome 21, beta amyloid precursor protein gene, autosomal dominant, with age of onset between 45 to 65 years.
Chromosomes 9, 10 and 12. These unknown genes have weak effects; they do not always cause the disease unless more than one is present and/or there is an environmental trigger.
Chromosome 19 has the apolipoprotein E gene that affects cell activity. The Apo-E gene found on chromosome 19 has three alleles: Apo-E2, Apo-E3 and Apo-E4. There is a tendency for people who have inherited two e 4 alleles to have an earlier onset of the disease than those who inherit one e 4 allele. People with one e 4 allele have an earlier onset of the disease than people with no e 4 allele. People who have inherited the e 2 allele have a tendency for a later onset of the disease.
It is worth noting that a person without the Apo-E4 allele can still develop Alzheimer's disease, and conversely, not everyone with the Apo-E4 allele will develop Alzheimer's disease.

What can be done if two or more people in one family have Alzheimer's disease?

The presence of more than one family member with Alzheimer's disease does not necessarily indicate that your family has one of the strongly-inherited forms of Alzheimer's disease.

It is essential to find out if suspected cases really are (or were) Alzheimer's disease. Contact an experienced clinical geneticist to confirm that the disease is transmitted through your family. This can only be done through a medical assessment. (Contact your local Alzheimer Society for a genetics clinic in your area.)

If the person is no longer living, the "best estimate" diagnosis can be determined through a careful review of autopsy reports and medical records, if available.

What are the implications of testing for genetic factors?

Researchers are now beginning to explore the immense psychological, legal, social and ethical implications of genetic testing. If genetic assessment or testing is done, it is critical that the person being tested fully understands these implications. The person should:

give informed consent to the testing
receive counselling from a trained professional
be guaranteed that the test results will remain confidential

If predictive tests prove reliable and become widely available in the future, it is very important that people who receive these tests are protected.

Resource:
St. George-Hyslop, P.H., "Piecing Together Alzheimer's," Scientific American, December 2000; 76-83, www.sciam.com .

Need further information?

Please refer to Alzheimer's Disease and Risk Factors

For more information on the ethical questions raised by testing, refer to Genetic Testing and Alzheimer's Disease.

Families with a history of Alzheimer's disease can inquire about participating in research through the:
Familial Alzheimer's Disease Registry
Centre for Research in Neurodegenerative Diseases
Tanz Neuroscience Building
University of Toronto
6 Queen's Park Crescent West
Toronto, ON M5S 3H2
www.utoronto.ca/crnd
e-mail: crnd.info@utoronto.ca