Mild Cognitive Impairment Symposium: Hunting for Genes Behind Neurodegenerative Diseases

Owen A. Ross, Ph.D.

Can genetic tests provide input for a diagnosis of Mild Cognitive Impairment (MCI)?  Dr. Owen Ross, Assistant Professor of Neuroscience at Mayo Clinic College of Medicine in Jacksonville, Florida gave a presentation on this topic at the MCI Symposium.

There’s a lot of interest in genetic testing to determine the risk of common diseases, including Alzheimer’s.  The day before the MCI Symposium started, ABC’s Nightline aired a piece on Alzheimer’s (see Part 1 and Part 2).  [Thanks to my friend Rich Bozanich for sending me a link to this.]  In Part 2 of the video report, Terry Moran, one of the program’s co-hosts, receives the results of his genetic testing.  His results indicate he has a 19% lifetime risk for developing Alzheimer’s.  As the piece ends, he and his wife are making plans for long term care arrangements.   In the same video, an Alzheimer’s advocate whose husband and mother have dementia opens the results of her genetic testing.  Her report says she has a 37% lifetime risk, and she says she will put her life in order.

Based on Dr. Ross’s presentation, making plans based on this kind of genetic testing seems premature.  Researchers are still working to identify genetic variations associated with most neurodegenerative diseases, including Parkinson’s and Alzheimer’s, he said.  Hundreds of genes are being studied in connection with these disorders.  However, as quickly as researchers report a new gene association, other researchers report that their studies do not confirm it. 

There are several reasons the search for these genes is so difficult, according to Dr. Ross.  First, the genes associated with the different neurodegenerative diseases vary widely, and second, even the genes that cause a specific disorder may vary.  For example, the genetic variations causing or contributing to Alzheimer’s in one person might not be the same as those in another person with Alzheimer’s.  Third, the effect of a genetic variation can differ across ethnicities. 

Fourth, it may be that extra copies of a normal gene are enough to increase the risk for or even cause neurodegenerative diseases.    Researchers at the Mayo Clinic and the National Institute on Aging have been following some people with an inherited form of Parkinson’s disease/Dementia with Lewy bodies who have three or even four copies (instead of the usual two) of the normal alpha-synuclein gene.  These extra copies of a normal gene, rather than a genetic variation or mutation of that gene, seem to be enough to cause the disease.  In the families studied, the more extra copies there were, the more severe the disease.

These findings could also apply to sporadic (non-inherited) neurodegenerative diseases, Dr. Ross explained in an email conversation after the Symposium.  It may be that even mild “over-expression” of genes – resulting in extra amounts of the proteins they encode – makes people susceptible to the diseases developed late in life. 

He says the interaction of genes with other factors may also make it hard to predict risk based on a simple genetic test.  “The expression of all genes is complex, with genetic factors and most likely certain environmental agents, affecting gene/protein expression,” says Dr. Ross.  “Age, stress and depression may be factors that alter gene expression, for example.”

What does all this mean about getting genetic tests for Mild Cognitive Impairment?  “At this point, unless you have a strong family history or early-onset age, genetic testing for Alzheimer’s, Parkinson’s or Mild Cognitive Impairment has little relevance,” says Dr. Ross.  [Genetic testing for research purposes would be an exception.]  He notes that even if you were found to have a gene that directly caused a neurodegenerative disease [as with rare early onset, inherited Alzheimer’s], there are currently no treatments for specific genetic forms of disease.

But he’s optimistic that with advances in DNA technology, many more genes associated with neurodegenerative diseases will be found, all with potential to cause or contribute to the different forms of Mild Cognitive Impairment.  “When the time is right, these genetic biomarkers will aid in early diagnosis and help determine the future of individualized therapy for each patient,” he says.

Comments

[Gail Rae Hudson]

I'm pleased that you highlighted, in this article, the growing concern among researchers that genetic research isn't as definitive as we've wanted to think. I, too, recently read an article that talked about the same situation. Genetic research, we're beginning to understand, isn't as simple as, say, a drone being programmed to hit a specified target. We're not even sure, at this point, what constitutes a target.
Good advice, at this point, that it's probably premature to "put one's life in order" when genetic testing, in its current state, reveals a 19% or 37% probability of disease.