Saturday, June 8, 2013

Late Onset Alzheimer's Disease (LOAD)

Alzheimer's disease is an irreversible, progressive brain disease. It is characterized by the development of amyloid plaques and neurofibrillary tangles, the loss of connections between nerve cells, or neurons, in the brain, and the death of these nerve cells. There are two types of Alzheimer's—early-onset and late-onset. Both types have a genetic component.

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Most cases of Alzheimer's are the late-onset form, which develops after age 60.

The causes of late-onset Alzheimer's are not yet completely understood, but they likely include a combination of genetic, environmental, and lifestyle factors that influence a person's risk for developing the disease.

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The single-gene mutations directly responsible for early-onset Alzheimer's disease do not seem to be involved in late-onset Alzheimer's.

Researchers have not found a specific gene that causes the late-onset form of the disease.

However, one genetic risk factor does appear to increase a person's risk of developing the disease. This increased risk is related to the apolipoprotein E (APOE) gene found on chromosome 19. APOE contains the instructions for making a protein that helps carry cholesterol and other types of fat in the bloodstream. APOE comes in several different forms, or alleles. Three forms—APOE ε2, APOE ε3, and APOE ε4—occur most frequently.

APOE ε2 is relatively rare and may provide some protection against the disease. If Alzheimer's disease occurs in a person with this allele, it develops later in life than it would in someone with the APOE ε4 gene.

APOE ε3, the most common allele, is believed to play a neutral role in the disease—neither decreasing nor increasing risk.

APOE ε4 is present in about 25 to 30 percent of the population and in about 40 percent of all people with late-onset Alzheimer's. People who develop Alzheimer's are more likely to have an APOE ε4 allele than people who do not develop the disease.

Dozens of studies have confirmed that the APOE ε4 allele increases the risk of developing Alzheimer's, but how that happens is not yet understood. These studies also help explain some of the variation in the age at which Alzheimer's disease develops, as people who inherit one or two APOE ε4 alleles tend to develop the disease at an earlier age than those who do not have any APOE ε4 alleles.

APOE ε4 is called a risk-factor gene because it increases a person's risk of developing the disease.

However, inheriting an APOE ε4 allele does not mean that a person will definitely develop Alzheimer's. Some people with one or two APOE ε4 alleles never get the disease, and others who develop Alzheimer's do not have any APOE ε4 alleles.

Using a relatively new approach called genome-wide association study (GWAS), researchers have identified a number of genes in addition to APOE ε4 that may increase a person's risk for late-onset Alzheimer's, including BIN1, CLU, PICALM, and CR1.

Finding genetic risk factors like these helps scientists better understand how Alzheimer's disease develops and identify possible treatments to study.

Source national Institute on Aging, Alzheimer's Disese Genetics Factsheet
http://www.nia.nih.gov/alzheimers/publication/alzheimers-disease-genetics-fact-sheet

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