The APOE Gene, Alzheimer's and Dementia

     Going through the thick folder containing Dad's medical records, I found the results of a genetic test:

Apolipoprotein E Genotype:  2 and 3.  Interpretation:  This individual does not possess an apoe 4 allele.  This result does not indicate whether this individual's dementia is due to Alzheimer's disease or other cause of dementia.

     The APOE or apolipoprotein E, gene makes a protein that carries cholesterol and other fats through the blood to be processed.  The three common variations of this gene are called e2, e3 and e4.  Everyone has two copies of this gene; Dad had one e2 and one e3 copy.  If you have one or two copies of the e4 variation, you may have a somewhat higher risk of developing Alzheimer's disease.

     But the connection between the APOE gene and Alzheimer's is not very strong.  Some people who don't have the e4 variation have Alzheimer's, and some people with Alzheimer's don't have the e4 variation.  My father didn't have the e4 variation, but still developed dementia.  The e2 variation he had is actually associated with a lower risk of developing Alzheimer's disease in some studies.

     The APOE gene may also influence the age at which people develop Alzheimer's.  People with the e4 variant who have Alzheimer's tend to develop it at a much earlier age than those who have Alzheimer's but not the e4 variant.  Even this influence is weak - in an article published in The American Journal of Human Genetics in 2000, researchers estimate that only 7 to 9% of the age of onset of Alzheimer's is explained by the e4 variation.

     Dad did not have the gene variation associated with higher risk of Alzheimer's

     Because the connection between the APOE gene and Alzheimer's or dementia isn't very strong, environmental factors and/or additional genes must play a role in determining whether someone develops dementia, and at what age.  The search for other genes involved with dementia is an intimidating task.  An overview of presentations at a recent conference on Alzheimer's notes that the AlzGene database of studies on genes and Alzheimer's contains information on over 300 candidate genes and 800 common variations.  So far, no one has found another gene that plays as significant a role as APOE.

     It could be a combination of genes determines whether or not someone will develop dementia.  For example, a study of 180 Alzheimer's patients and 120 non-demented volunteers identified three different gene combinations, each of which appeared to increase the risk of developing Alzheimer's by 800 percent for study participants.

     The US National Institute on Aging is sponsoring ongoing research to identify genes involved in Alzheimer's.  The study is recruiting siblings, at least one of whom must have been diagnosed with the disease.

     If the link between genes and dementia were better understood, genetic tests could be used to predict, diagnose and maybe even treat Alzheimer's and other dementias.  In the meantime, the association between the APOE gene and Alzheimer's isn't strong enough to be useful.  Testing for the e4 variation of the APOE gene didn't help us understand Dad's dementia at all.