ALZHEIMER'S AGE OF ONSET, CAUSES, IMPLICATIONS

When the University of Washington's Alzheimer's Disease Research Center did its study of dominantly inherited Alzheimer's disease, looking for the gene that affects our family and other Volga German families (families who left Germany in the 1760's, lived in Russia along the Volga for a hundred years or more, then came to North America), they ultimately identified 11 VG families with familial Alzheimer's who carry the PS2 gene. The study showed a wide variation in the average age of onset within the 11 families. Our family's average age of onset was 51, and there was one family with an age of onset in the early 70's. The primary cause of this variation in age of onset is another gene. It is ApoE4. This gene is not the only factor. There are likely other genes with less impact on the age of onset than ApoE4. Two new ones have recently been identified that may act in conjunction with ApoE4.

Each child inherits one Allele of ApoE, either 2, 3, or 4, from each parent. Number 2 seems to be positive, increases the average age of onset of Alzheimer's, number 3 seems to be neutral, and number 4 lowers the age of onset. ApoE4 was very prominent in my father's generation, and seems to account for the low average age of onset of the disease. Many of that generation had two 4's. Such was the case with Uncle Oliver, who did not have PS2, but had clear symptoms of Alzheimer's by age 68 and died at 78.

My dad was 100% Volga German. Both his father and mother carried at least 1 ApoE4 and so they passed either 1 or 2 to the next generation. My dad's great, great grandchildren are now being born. They are only 1/16 Volga German. While that does not affect whether or not one inherits the dominant PS2 gene, it seems probable that the frequency of ApoE4's in the family has decreased dramatically since my father's generation, theoretically raising the age of onset of Alzheimer's caused by PS2. This may not be a total comfort to those in line for PS2. However, having symptoms at age 65 is certainly better than at age 55. If this hypothesis is true, the age of onset in our family is rising, the change could be a factor in such decisions as whether or not to have children and whether or not to be tested for PS2.

ApoE does not cause Alzheimer's. It is a "susceptibility" gene, increasing the likelihood that the one who carries the gene will get Alzheimer's, but not everyone who has the gene gets the disease. This gene appears to be affected by environmental factors, as well as by other factors unknown. Dr. William Klunk of the University of Pittsburgh pointed out in his endorsement of THE THOUSAND MILE STARE that nearly 50% of people who reach the age of 85 have Alzheimer's. In my case, I have 1 copy of ApoE4 so I have approximately a 50/50 chance of having Alzheimer's by age 80 instead of 85.

For me, the additional time I gained when PS2 skipped me seems like bonus time. While I don't relish the thought that ApoE4 may lower the age of onset if Alzheimer's comes, I want to make the most of the time I have. That's the least we can do to honor those who have already suffered and died.