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Genetic Components of AD

Genetic Components of AD

Alzheimer’s disease patients develop neuritic plaques consisting of a dense core of proteins known as beta (β) amyloid. These areas are then enveloped by degenerating axons and dendrites, in addition to activated microglia and reactive astrocytes (Carlson, 1999).  Eventually, the phagocytic glial cells destroy the degenerating axons and dendrites, leaving only a core of β amyloid. The products of amyloid precursor protein (APP) genes and the presinilin genes all cause defective forms of β amyloid to be produced. Alzheimer’s patients can also develop neurofibrillary tangles (on dying neurons) containing intracellular accumulations of twisted protein filaments that previously served as the cells’ internal skeleton (Carlson, 1999). Many researchers believe that a defective production of β amyloid causes these neuritic plaques to develop. Normal β amyloid (short form) contains 40 amino acids, whereas defective β amyloid (long form) mutates to consist of 42 to 43 amino acids. The 21st chromosome contains a gene that produces the beta APP, which consists of a long chain of amino acids that is cut apart by enzymes to produce β amyloid. Where the cut happens on this chain determines whether a normal or defective form of β amyloid is produced. As a result, researchers have been able to identify that Alzheimer’s gene mutations occur because of APP gene on chromosome 21, presinilin-1 on chromosome 14, and presinilin-2 on chromosome 1 (Lovestone, 1999). Neuropil threads are another major component of AD, and are composed of the microtubule-associated protein tau that has undergone posttranslational modifications. These threads cause further neuron disruptions and are speculated to accumulate until tangles develop (Miyasaka et al., 2005; Schmidt, Murray, & Trojanowski, 1993).

AD can be connected to a gene on chromosome 19 called the APO E gene, which codes for protein apolipoprotein E. This protein is responsible for the movement of cholesterol in and out of the body’s cells. There are, however, three forms of APO E gene. APO E2, E3 and E4. Every human has two copies of this gene, one from each parent. E3 is reported to be very common, occurring in 40-90% of the population, whereas E2 is found in 2% population and E4 in 6 to 37% of the population (Foster, 2002). Current research reports that individuals with the APO E4 allele inherited from both parents have a 15-time greater risk of developing Alzheimer’s than someone without (Foster, 2002). Because of these genetic links to this disease there have been connections made to a hereditary component. However, most forms of AD are not hereditary; it is observed to be present in only 5% of the population over 65 (Carlson, 1999). Therefore, there has been much speculation around the root cause of the production of these beta amyloid plaques. For instance researchers have suggested that production of β amyloid plaques may occur when an individual comes in contact with toxic substances, such as the amount of aluminium one absorbs, triggering the mutation of β amyloid (Foster, 2002). Additional theories/risk factors suggest that AD may be related to gender, lack of education, malnutrition, head injuries, infections, excessive alcohol use, or drugs. The key element to understand is that researchers have to date been unsuccessful in explaining the how and why of Alzheimer’s.

However, a number of theories on how to treat this disease, and research in this area is expansive and progressive

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