Genotyping and Endocrinology Clinical Services:
Risk Factor Genes__
1. ApoE - The Apolipoprotein E gene is located on chromosome 19 and the APOE protein is responsible for transporting cholesterol and fats between cells and absorbing cholesterol from foods in the intestine. The most common ApoE genotype is e3/e3, which occurs in 40 - 90 percent of people. The e2 allele is rare, occurring in only 2 percent of the population. The e4 allele is found in 22 percent of the world population: 20 % with the e3/e4 genotype and 2% with the e4/e4 genotype). However, this allele occurs in 60 % of individuals that will develop Alzheimer's disease (~15 % with e4/e4, 40 % with e3/e4 and < 5 % with e2/e4). The association of apoE e4 allele and AD holds true for both sexes, but there are reports that suggests a higher frequency of e4 alleles in women compared to men (Poirier, 1993). Corder and colleagues reported that nearly 100% of women aged 85, and with one dose of e4, were affected with AD compared to only 50% of men, but they did not consider this significant due to the small sample size (Corder et. al., 1995). For individuals who consume high-cholesterol diets, possessing the e4 allele may also increase the risk of coronary artery disease and stroke. The presence of the apoE genotype is the most important genetic risk factors for AD by different researchers in the field.
In general, ApoE is involved in triglyceride, phospholipid, cholesteryl ester, and cholesterol transport in and out of cells (Mahley, 1988). It facilitates cholesterol removal from the plasma and cerebrospinal fluid (CSF) (Poirier, 1994, 1996). In the peripheral nervous system (PNS), it has been shown to assist in the mobilization and redistribution of cholesterol in repair, growth, and maintenance of myelin and neuronal membranes during development and injury (Mahley, 1988; Poirier, 1994). Studies using the rat brain have shown that in the CNS, apoE is important in the metabolism and redistribution of cholesterol and phospholipids during myelination and membrane remodeling associated with axonal regeneration (Beffert, et.al. 1998; Poirier, 1994).
For reviews on ApoE epidemiology please see the following links -
» APOE Genotype Effects on Alzheimer's Disease Onset and Epidemiology
3. Matrix Metalloproteins