In the Alzheimer’s disease field, scientists have made great advances in identifying specific genetic markers that increase a person’s risk of developing Alzheimer’s and related diseases. Here are a few Alzheimer’s scientists on the forefront of genetics research who are addressing this important topic:
Jason Karlawish, MD
University of Pennsylvania
Jennifer Yokoyama, PhD
Memory and Aging Center at UCSF
Duygu Tosun, PhD
One of the most well-known risk factors for Alzheimer’s is the ApoE gene. There are three forms, or alleles, of the gene: ApoE-ε2, ApoE-ε3, and ApoE-ε4, with the ApoE-ε4 allele giving the highest risk for developing late-onset Alzheimer’s disease. Testing for ApoE genotype is not part of routine healthcare, but a number of new clinical trials are testing for ApoE status as part of their screening process. This brings up an important issue—Is it ethical to inform people about their ApoE genotype? Jason Karlawish, MD, a physician, researcher, and bioethicist at the University of Pennsylvania, has designed a process to assist a person in deciding whether they want to know their result, and to assist the clinical investigator to decide whether to perform the test. Karlawish explains the ethical justification for this practice, “It makes sense to learn an ApoE result in the context of a study testing a therapy that will be prescribed to people with a particular genotype. The trial allows us to understand the experience of learning the gene results and taking the drug. This is as close to future clinical practice as we can get and so valuable to science.”
Dr. Karlawish has also reported on important potential consequences of ApoE genotype disclosure in clinical trials. On the positive side, participating in a clinical trial may have direct benefits on a person’s health, and also has many potential indirect benefits, particularly the satisfaction of helping to discover new ways to treat Alzheimer’s disease. On the other hand, knowing you’re at risk may cause short term distress and emotional burdens for that individual and their family. “We’re finding that this is the kind of information that ramifies into people’s families and their social network. People are concerned that others may treat them differently than they did before they knew this result.” Dr. Karlawish and others are encouraging scientists to carefully discuss these pros and cons with people who are considering learning their ApoE result.
In addition to APOE-ε4, there are many other genes that contribute modest risk for developing Alzheimer’s disease. Researchers like Jennifer Yokoyama, PhD, a geneticist and neuroscientist at the Memory and Aging Center at UCSF, are trying to understand how variation across an individual’s entire genome affects their risk for developing diseases like Alzheimer’s. She and collaborator, Rahul Desikan, MD, PhD, a UCSF radiologist and researcher, are studying the impact of polygenic—or the contribution of multiple genes—risk for developing Alzheimer’s disease in an age-specific manner. “The predictive potential of genetic information will be critical for us to effectively assess and, ultimately, administer future treatments that are able to slow or prevent the development of Alzheimer’s disease.”
A growing body of evidence demonstrates that genetic risk differs in men and women. For example, ApoE-ε4 genotype confers greater risk for developing mild cognitive impairment and Alzheimer’s disease in women than in men. But why? Recent studies suggest this may be due to the way that ApoE affects the deposition of amyloid and tau in the brain, two proteins thought to be responsible for causing dementia. Radiologist Duygu Tosun, PhD, an expert on Alzheimer’s brain imaging at UCSF, is further delving into this important topic in a project funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI). “Women were found to have more amyloid plaque in their brains than men of the same age and same cognitive ability, at every stage of the disease,” said Dr. Tosun. “This was the case regardless of whether the women carried the ApoE-ε4 gene.”
These lines of research emphasize the growing importance of genetics studies in advancing brain health. At the Brain Health Registry, we are excited to announce the launch of GenePool, the Brain Health Registry’s own genetic study. In the next few months, we will begin a small pilot study in which we will collect genetic material from some BHR participants using mailed saliva kits. Before we launch this new study, we hope to better understand your motivations for, and concerns about, participating in genetic studies. All BHR participants will soon receive an invitation to complete a new BHR questionnaire, called “Genetic Study Interest”. We hope you will complete this new questionnaire and continue to engage with us in our efforts to advance brain health research!