Alzheimer’s Disease: The Genetic Factors for early/late onset
Genetics and Early Onset Alzheimer’s Disease
There are two types of Alzheimer’s disease – early onset and late onset. Early onset Alzheimer’s is also called familial Alzheimer’s because it runs in families. It is genetic in origin. A significant proportion of early onset Alzheimer’s is linked to three genes: presenilin 1, presenilin 2 and A-Beta or amyloid precursor protein. If you have one of these three genes, it would be very unusual not to develop Alzheimer’s before the age of 65.
Early onset Alzheimer’s is defined as Alzheimer’s that strikes people before the age of 60 to 65 years and often before the age of 55. It has been known to develop between the ages of 30 and 40, but that is exceedingly rare. Early onset is most common in someone in their 50s. Early onset Alzheimer’s is a rare form of dementia. Only 6 to 8 percent of all people who have Alzheimer’s have this early onset form.
Late Onset Alzheimer’s and The Apoe-e4 Gene
In contrast to early onset Alzheimer’s disease, late onset Alzheimer’s has no known cause and shows no obvious inheritance pattern. For this reason it is also called sporadic Alzheimer’s disease. The only risk factor gene identified so far for late onset Alzheimer’s disease is a gene that makes one form of a protein called apolipoprotein E (ApoE). Everyone has ApoE, which helps carry cholesterol in the blood. There are three forms of the ApoE gene. Different forms of the same gene are called alleles. The three alleles of the ApoE gene are known as e2, e3 and e4. Everyone receives one of these three alleles from each parent. Thus the possible combinations in one person are e2-e2, e2-e3, e2-e4, e3-e3, e3-e4, e4-e4.
Having one or two copies of the e4 allele increases a person’s risk of getting Alzheimer’s, but it does not mean that Alzheimer’s is certain. Some people with two copies of the e4 allele (the highest risk group) do not develop clinical signs of Alzheimer’s disease, while others with no e4 do. The ApoE-e3 allele is the most common form found in the general population and may play a neutral role in Alzheimer’s disease. ApoE-e2 is the least common form and appears to be associated with a lower risk of Alzheimer’s.
What Is The Risk?
About 15 percent of the general population has the ApoE-e4 allele, and about 40 percent of people with Alzheimer’s disease do. Thus, the gene for the ApoE-e4 allele is found about three times as frequently in persons with sporadic Alzheimer’s as in age-matched control subjects. But the exact degree of risk for any given person cannot be determined based on ApoE status.
Therefore, as was previously noted, inheriting the ApoE-e4 allele doesn’t mean that a person has a certainty of developing Alzheimer’s. Some people with the gene never develop Alzheimer’s, and, conversely, there are people with Alzheimer’s who do not have the gene. Thus, ApoE-e4 is called a risk factor gene for late onset Alzheimer’s disease. It is not predictive.
Next week’s article will discuss two epidemiological studies that explore the question of whether Alzheimer’s disease is genetic or environmental in origin, or both, and whether environment can modify genetics.
Mary Lou Williams, M. Ed., is a lecturer and writer in the field of nutrition. She welcomes inquiries. She can be reached at (239) 267-6480.
By Mary Lou Williams, M. Ed.