DNA Alzheimer’s Disease Risk Test

Alzheimer’s is a neurodegenerative disease, and the initial changes in the brain occur long before any visible symptoms are observed. Two abnormal protein accumulations (amyloid plaques and tau tangles) form in the brains of affected patients. The plaques prevent the normal connections and communication between the billions of neurons in the brain, while the tau tangles disrupt the normal movement of nutrients and other essential supplies within each neuron. These abnormalities lead to cell death and brain shrinkage, and eventually patients begin to show outward signs of Alzheimer’s disease. The early stages are characterized by memory loss, misplacing items, challenges in planning or solving problems, difficulties performing familiar tasks, poor judgment, personality changes and confusion with time or place. As the disease progresses, patients begin to have trouble recognizing family and friends and are unable to learn new things, or become distressed in new environments. Other symptoms at the mid-stage of Alzheimer’s can include hallucinations, agitation, delusions and paranoia. In the final stages of Alzheimer’s disease, patients are unable to communicate and must rely of others for everyday care. They become bedridden and the body shuts down, usually resulting in death from general inanition, malnutrition or pneumonia.

The causes of Alzheimer’s disease are not fully understood, and many genetic and environmental conditions are likely to contribute. One strong genetic risk factor for late-onset Alzheimer’s is the e4 form of the APOE gene. The APOE gene encodes Apolipoprotein E, a protein involved in injury repair and transporting fats between brain cells. Individuals that have one copy of the e4 allele have a 3-fold increased risk of developing Alzheimer’s, while e4 homozygotes (two copies of e4) have up to a 15-fold increased risk. Other risk factors for Alzheimer’s include other health issues (e.g. diabetes, cardiovascular disease, high blood pressure and high cholesterol), lifestyle choices (smoking and excess alcohol), cognitive and physical inactivity, and head trauma.

The APOE gene is located on chromosome 19. There are three forms or alleles of APOE – e2, e3 and e4. One allele is inherited from each parent, resulting in six possible combinations: e2/e2, e3/e3, e4/e4, e2/e3, e2/e4 or e3/e4. The presence of the e4 allele is linked to an increased risk of Alzheimer’s disease, whereas the e2 allele has a protective affect.

A simple DNA test can be completed to determine which alleles of APOE an individual carries. The three alleles are e2, e3 and e4. Each person can inherit two identical alleles or two different alleles of APOE.

• e4/e4 – Two copies of the e4 allele is associated with a 10- to 15-fold increased risk.
• e3/e4 or e2/e4 – A single copy of e4 increases the risk by 3-fold.
• e3/e3 – The presence of two copies of the common e3 neutral allele does not affect the risk.
• e2/e2 or e2/e3 – Inheriting one or two copies of e2 is protective and reduces the risk.

Alzheimer’s Disease Fact Sheet. Alzheimer’s Disease Education and Referral (ADEAR) Center – A service of the National Institute on Aging, National Institutes of Health.

Leal SL, Yassa MA (2013). Perturbations of neural circuitry in aging, mild cognitive impairment, and Alzheimer’s disease. Ageing Research Reviews. 12(3): 823-31.

Goldman JS et al. (2011). Genetic Counseling and Testing for Alzheimer Disease: Joint Practice Guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genetics in Medicine, 13(6): 597-605.