Sporadic Alzheimer’s, also known as Late Onset Alzheimer’s, is the most common form of Alzheimer’s by far, and tends to occur much later in life than FAD. That is, it can affect adults of any age, but it usually occurs after age 65.
This form Alzheimer’s can affect people who may or may not have a family history of the disease. There is currently no evidence that autosomal dominant inheritance of mutated genes causes Sporadic or Late Onset Alzheimer’s. However, genetics does appear to play a significant role in the development of this far more common form of the disease.
Different variations, or alleles, of particular genes produce variations in inherited characteristics, such as height, skin color, eye color, blood type, and so on. In the early 1990s, researchers at Duke University in Durham, North Carolina, found an increased risk for late-onset Alzheimer’s in people who inherited one or two copies of a particular variation of a gene called apolipoprotein E (APOE) – the variation known as APOE e4.
Apolipoprotein E is a protein that has various functions, such as helping the blood to carry cholesterol throughout the body.
This protein was found in neurons and other supportive brain cells (called glia) of healthy brains, but it is also found in excessive amounts with the plaques found in the brains of people with Alzheimer’s.
Researchers are particularly interested in three common alleles of the APOE gene: e2, e3 and e4.
There is evidence to suggest that the relatively rare APOE e2 allele may protect some people against the disease because it seems to be associated with a lower risk for Alzheimer’s and a later age of onset if the disease does develop.
The APOE e3 allele is the most common version of APOE found in the general population and current evidence suggests that it plays a neutral role in Alzheimer’s risk.
The discovery that increased an risk is associated with the inheritance of the APOE e4 allele has helped explain why there are some of the variations in age of onset of Alzheimer’s disease based on whether people have inherited zero, one, or two copies of the APOE e4 allele from their parents. The more APOE e4 alleles inherited, the lower the age of disease onset.
The inheritance of one or two APOE e4 alleles does not guarantee that the person will definitely develop Alzheimer’s. That is, unlike early-onset FAD, a person can have one or two APOE e4 alleles and still not get the disease.
In addition, a person who develops the disease may not have any APOE e4 alleles. APOE e4 seems to increases the risk of developing Alzheimer’s, but it does not cause the disease.
The ways in which APOE e4 increases the likelihood of developing Alzheimer’s are not currently known with any certainty. However, APOE e4 does facilitate beta amyloid buildup in plaques and this seems to contribute to lowering the age of onset of the disease. Other theories involve interactions with cholesterol levels and effects on nerve cell death that are independent of its effects on plaque buildup.
Studies over the last few years indicate that there are additional risk factor genes for late-onset Alzheimer’s, and candidates continue to be identified in this area of research. Using high blood levels of beta amyloid as a marker of a genetic defect, several research groups have reported compelling evidence that a region on chromosome 10 may contain another gene linked with Alzheimer’s.