The Genetics of Alzheimer's Disease: Are You at Risk?

Neurology Now
Fall 2005
Volume 1(3)
p 42–43
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If your mother, father, or grandparent has Alzheimer's disease (AD) are you also at risk?

Genetic screening may be able to tell you, but experts say it should only be used under specific circumstances.

“No one should be screened for Alzheimer's disease unless there is a very specific family history of the condition,” says Jill Goldman, M.S., a genetic counselor at the University of San Francisco Memory and Aging Center.

Genetic testing requires several one-on-one counseling sessions with a specially trained counselor, she adds. This counseling is necessary because the genetics of AD is complicated. “There are many genes we know are involved, and others we may not know about — and we don't have enough information about how different genes impact one another to easily determine risk,” she says.

In addition, counseling may be needed to help people grapple with the knowledge that they have an increased risk of a disease that is currently not preventable. While you may be armed with information about your genetic makeup, “there's nothing you can do in terms of preventing the disease,” says Thomas Bird, M.D., chief of the division of Neurogenetics at the University of Washington in Seattle. “The most valuable use of genetic screening under these circumstances is for family planning, financial planning and career planning.”

Late Onset AD

Age is the most important risk factor for Alzheimer's disease, a progressive, neurodegenerative disease characterized in the brain by abnormal clumps (amyloid plaques) and tangled bundles of fibers (neurofibrillary tangles) composed of misplaced proteins.

The most common form of AD is late-onset, meaning it develops after age 65; the number of people with the disease doubles every five years beyond that age. Only one gene has been identified so far as a risk factor for late-onset AD — a form of a protein called apolipoprotein E (APOE), which helps carry cholesterol in the blood. Researchers have found that the e4 type, or APOE e4, is associated with an increased number of amyloid plaques deposited in the brain.

Estimates of how great that increased risk is vary, so genetics experts are reluctant to give it a specific number. For example, a 2003 study in the New England Journal of Medicine estimated that inheriting a single copy of the APOE e4 gene may increase the risk by 50 percent over a lifetime. An earlier study (1997) in the Journal of the American Medical Association found that patients with two copies of the APOE e4 gene were nearly 15 times more likely to develop AD, whereas those with one copy were 2.6 to 3.2 times as likely. Not everyone with AD has the APOE e4 gene, and not everyone who has APOE e4 will develop AD. There is a commercially available test for the APOE e4 gene, but people should not take it unless they are experiencing disease symptoms, says Goldman. (See Box: Symptoms of AD.)

Box. Symptoms of Alzheimer's Disease

Click here to enlarge

Early Onset AD

Early-onset or familial AD — which affects only five percent of patients — is inherited and typically develops between the ages of 30 and 60, says Goldman. Researchers have identified three specific inherited gene mutations — alterations in the DNA of the genes that prevent them from working as they normally would — for early-onset AD: amyloid precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2).

If you have a parent with one of these gene mutations, you have a 50-50 chance of developing AD, explains Dr. Bird. If you have one of these mutations, you can get the disease as early as your 30s or 40s, he adds.

If your mother, father, sister or brother developed AD before the age of 60 and have symptoms of the disease, you should consider getting being tested for PS1. PS1 accounts for 50 percent of familial early-onset AD. There is a commercially available test to screen for the PSI gene.

If doctors do not find the PS1 mutation, you might consider being screened for the PS2 and APP genes. Goldman notes, however, that this is only currently being done in research trials. To find out more about those trials, go to the National Institute Aging at www.nia.nih.gov or http://clinicaltrials.gov .

If you suspect you have an inherited form of AD — and are not sure what to do — seek out advice from an expert before taking any test. “You need to consult with a genetic counselor or a doctor who is very knowledgeable about genetics and not go into this blindly,” Goldman says. To find a genetics counselor, ask your neurologist or contact the National Society of Genetics Counselors at (610) 872-7608 or visit www.nsgc.org .

FOR MORE INFORMATION

American Academy of Neurology Foundation

The Brain Matters

www.thebrainmatters.org

Alzheimer's Disease Education and Referral Center

(800) 438-4380, (301) 495-3311

www.alzheimers.org

Alzheimer's Association

(800) 272-3900, (312) 335-8700

www.alz.org

National Family Caregivers Association

(800) 896-3650, (301) 942-6430

www.thefamilycaregiver.org

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