Everyone has an ApoE4 gene as this gene is involved in the transport of cholesterol in and out of cells. In general, this gene facilitates the removal of cholesterol from plasma. The two other versions of this gene are ApoE2 and ApoE3. The ApoE3 is the most common in the general population. It is known that everyone inherits 2 of these ApoE genes, one from each parent. The ApoE4 gene is seen in two-thirds of late-onset Alzheimer's patients, but this is not limited to only people with a family history of the disease. The risk associated with having this gene is three times greater than for the general population.
Percentage of population with symptoms below 70 year of age:
Though the ApoE gene is located in all neurons of both healthy and AD patients, it has been noted that the ApoE gene is localized in the senile plaques and neurofibrillary tangles that are seen in the affected persons. The presence of the ApoE4 seemed to best predict whose condition would decline, as this gene appears to mark susceptibility to AD. One may have this gene and never develop the disease, while a person can get the disease and never have the gene.
It interesting to note that the rare ApoE2 gene may actually prevent or decrease the risk of developing the disease or increase the age of onset. A person with one ApoE2 gene and one ApoE3 have only one fourth the risk of developing the disease compared to a person with two ApoE3 genes.
The function of the ApoE4 gene is to produce a protein that will bind tightly to beta-amyloid, which is the ApoE3 protein. ß-amyloid is normally soluble, but when the ApoE4 protein latches on, it becomes insoluble and more likely to be deposited in the plaques. It is suggested that the ApoE4 increases deposits of ß-amyloid. Another theory is that the presence of ApoE in neurons affects certain cell processes and how synapses function. There have been marked differences in the rates at which ApoE3 and ApoE4 bind to tau protein and also to a similar protein in dendrites. It is speculated that the ApoE4 product allows the microtubule structure to come undone, leading to the observes neurofibrillary tangles.
The next step in research of this area is to see how tau protein and beta-amyloid protein react with the ApoE in its many forms, and also to determine the actions and roles of ApoE. If somehow the ApoE2 turns out to be beneficial, then substances that mimic its effect could be developed to help slow or prevent the progress of AD. There has been some interesting ideas relating to how ApoE4 affects structures other than proteins. In patients with the ApoE4 gene, the dendrites tend to be shorter, as a result of some unknown agent. The implied result may be that these pruned dendrites may not be able to form as many connections with other neurons. These neurons with shorter dendrites can occur in people without the ApoE4 gene, however, it seems to happen 20 to 30 years earlier in people with the ApoE4 gene.