Genes-R-Us — Genetics of Alzheimer’s disease
Posted: Wednesday, January 18, 2012 5:00 pm
The most common cause of dementia in the elderly population is Alzheimer’s disease (AD). The number diagnosed doubles between age 79 and age 84, and then doubles again between age 85 and age 90, according to my direct-to-consumer (DTC) genetic testing report.
Dr. Rudolph Tanzi, a well-respected leader in Alzheimer’s research, says that every 72 seconds a new diagnosis of AD is made and that an estimated 40 percent of people over the age of 85 have it.
Tanzi also states that by the year 2020, the aging baby boomers will triple the current cases of AD. If that projection is correct, then AD is poised to become a national disaster — not just personally devastating but economically crippling.
As a nation, we spend 400 times more on caring for those with AD than we do on research. There are no drugs to treat AD; the drugs that we do have only lessen some symptoms but do not prevent or stop the disease. Dr. Tanzi posits that if we were all to live to 120 years of age, we would all develop AD.
There is no simple medical test for AD. Formal diagnosis is only made post-mortem through an autopsy, which is often not performed.
If someone develops the disease before age 60, then it is termed early-onset as opposed to late-onset AD. But in either case, the disease process starts in the brain decades before any symptoms are observed.
The disease is characterized by amyloid beta plaques and tau tangles in the brains of its victims — two proteins gone haywire. (youtube.com/watch?v=NjgBnx1jVIU)
What do we know about the genetics of Alzheimer’s?
Three genes (including the gene that makes a precursor protein to amyloid beta) have been linked to early-onset familial AD. Inheriting any one of several hundred mutations in any one of three genes is sufficient to trigger the disease. This familial early-onset Alzheimer’s represents about 10 percent of the cases.
With the advent of cheap genomics, scientists now realize that there are a whole host of genetic mutations that occur rarely, but when they do AD is the result. But each of these new genetic mutations explains only a fraction of the cases.
The most important known genetic risk for late-onset AD hinges on the APOE gene. APOE is involved in the regulation of triglycerides and is now recognized to have an immune system function. But exactly how the variants in the APOE gene modulate the risk for AD is not fully understood.
APOE has three variants are called e2, e3, e4. We get a variant of APOE from each parent.
I received an e3 version from each parent. I am, thusly, e3/e3, as are an estimated 67 percent of those of European heritage. APOE e3 is considered risk neutral for AD.
APOE e4 is associated with an increased risk; for those who do develop AD, it is also associated with developing late-onset AD at an earlier age. An estimated 1.7 percent of those of European heritage are e4/e4, with 19 percent being e3/e4.
The risk increases from four to 12 times, depending upon inheritance of one or two copies of e4 from one’s parents.
Over half of those with these high risk variants of APOE never develop Alzheimer’s. So, although the risk is clearly higher, there are other important factors that research has yet to reveal.
APOE _2 is a rare variant that may have protective effects against AD. But less that one percent of the European population is estimated to be e2/e2 and 1.7 percent at e2/e3. The e2/e4 variant of APOE has never been observed. And then there are the sporadic cases of AD with no family history or any known genetic risk.
Some people don’t want to know their risk for AD. But I am a planner. I would rather spend my existing neuronal connections on planning rather than on unfocused worrying.
Editor’s note: Nancy Miller Latimer has worked in scientific research and development for 27 years. She blogs at neuronalbeauty.blogspot.com. Published in The Messenger 1.18.12