Alzheimer's Disease

Alzheimer’s Disease affects older patients but I have heard it is linked to genetics. Are there any recent studies associated with this disease? If so, please update my information! Biology Student in Ann Butlers class, Cambridge Academy

Alzheimer’s disease (AD) is the most common cause of dementia affecting persons over 65. It is estimated that over 4 million people in the USA suffer from AD, and that it occurs in nearly half of all people aged 85 years and older. The disease affects the parts of the brain that control thought, memory and language. Early signs of AD, such as simple forgetfulness, are subtle. As the disease progresses, typically over a 5-15 year span, more noticeable memory loss, and changes in behavior, personality, and judgement occur. People with advancing stages of AD soon forget how to do even simple tasks, such as brushing their teeth or speaking clearly. Eventually, they may need total care.

A clinical diagnosis is accurate in 80-90% of patients. However, only upon autopsy examination can one confirm the diagnosis of AD. Changes seen in the cortex of the brain include the loss of neurons, and the accumulation of abnormal proteins, creating neurofibrillary (neuro-fi-bril-lary) tangles and amyloid (a-mi-loyd) placques.

Early onset (before 60 years of age) and inherited forms of AD have been reported in rare instances. At least 3 genes have been found to be the cause of AD in these families. The Presenilin 1 gene, on chromosome 14, may account for the majority (60%) of the early-onset cases. A second gene, APP, codes for the abnormal protein forming the amyloid placques; APP resides on chromosome 21. Changes in this gene are seen in less than 20 families in the world literature. Likewise, in a small subset of families of Volga German origin, a gene has been identified on chromosome 1, which normally codes for a protein called Presenilin 2. Although still unproven, changes in either of these genes may directly or indirectly affect the rate and formation of the amyloid placques seen within the brain tissue of AD. These 3 Alzheimer’s disease genes explain only a small percentage (<2%) of all Alzheimer disease cases.

The role of genetics in the more common, later-onset AD is less clear. It has been known for some time that having a family member with the disease increases one’s own risk several fold. Numerous studies, in different racial and ethnic populations, have now confirmed that there may be several genetic markers for susceptibility to the adult-onset AD. One such marker is Apolipoprotein E (APOE), a protein involved with cholesterol transport in the body. It was recently observed that certain common forms of the APOE gene, specifically known as the E2, E3 and E4 markers, have a strong role in determining one’s lifetime risk for Alzheimer’s disease. For instance, genetic testing has shown that individuals who carry 2 copies of the E4 marker have, in general, an earlier age of onset and a threefold increased risk for AD, than those individuals with 1 or no copies of this marker. About 75% of late onset AD cases show the E4 marker. In contrast, carrying the E2 or E3 marker of this gene may actually decrease your individual risk for AD. It is important to note that not everyone who possesses the E4 marker will develop the illness. Other factors such as an individuals family history, sex, serious head injury, smoking, and cholesterol level may also influence the APOE risk.

Further understanding of the precise disease mechanism, as well as identifying the role of other genetic and environmental factors, will improve the diagnosis and treatment of Alzheimer’s disease. Please contact the Alzheimer’s Association, (800) 272-3900 for further information.