A new Alzheimer’s research program aims to accelerate the recruitment of people interested in volunteering for Alzheimer’s studies based on genetic risk factors.
GeneMatch, created and administered by the Banner Alzheimer’s Institute, Phoenix, will be a key part of the research toward finding an intervention to slow or stop the development of Alzheimer’s disease in people who carry the high-risk variant of the apolipoprotein E gene (APOE). By creating a large pool of cognitively healthy subjects who are already stratified by APOE status, GeneMatch can accelerate enrollment in studies targeting those with the highest-risk allele, APOE epsilon-4 (APOE4).
“Research studies in healthy people at different levels of genetic risk for Alzheimer’s promise to further clarify the earliest biological changes associated with the disease, clarify what genetic risk disclosure means to people in the new era of Alzheimer’s prevention trials, and find effective treatments to end Alzheimer’s as quickly as possible,” said Dr. Eric Reiman, executive director at Banner and codirector of the Alzheimer’s Prevention Initiative, of which GeneMatch is a part. “GeneMatch is intended to provide an unprecedented resource of genetically characterized research volunteers to do just that.”
Dr. Eric Reiman
Because at least one APOE4 allele is carried by about 14% in the general population, recruiting a sufficient number of these subjects for studies can take years. Having a pool of prescreened subjects should make the process much easier, much quicker, and much less expensive, according to Dr. Pierre N. Tariot, director of the institute.
For example, Dr. Tariot said during a teleconference, the upcoming Alzheimer’s Prevention Initiative APOE4 Trialneeds about 1,300 cognitively normal people who carry two copies of the APOE4 allele. That genetic combination – the most aggressive risk factor for late-onset Alzheimer’s – occurs in less than 2% of the general population.
“We would need to genotype tens of thousands of people to end up with that many participants,” Dr. Tariot said. GeneMatch should lower the screening number from tens of thousands to thousands, he said.
In fact, the API APOE4 Trial, which will test both the anti-amyloid antibody crenezumab and a beta-secretase inhibitor in homozygous APOE4 carriers, will be the first one to use GeneMatch along with traditional recruitment methods, Dr. Tariot said. Other Alzheimer’s studies with a genetic component may also take advantage of the subject pool because it will be a shared resource.
Dr. Pierre N. Tariot
The GeneMatch program grew from the challenge researchers faced in recruiting enough subjects for the API APOE4 trial, Dr. Reiman said.
“We decided to conduct these screening tests in a way to benefit the entire AD research community,” he said. “We hope this shared resource will help researchers clarify the earliest brain changes, any protective factors for APOE4, and contribute to a growing number of prevention trials and find something that will work to delay or stop Alzheimer’s onset within the next 10 years. We really think this will dramatically shift how researches conduct trials, reducing the number of volunteers we need to recruit and saving time and money.”
“Recruiting to prevention trials based on genetic risk provides a major advantage since risk can be roughly quantified and major subgroups responses identified,” said Dr. Richard J. Caselli, when asked to comment on the new program. “Biomarker evidence is another approach, but one can question how presymptomatic someone with a head full of amyloid really is, especially over the usual recruitment ages. GeneMatch seems to be the first mass genetic screening and registry program in the U.S. and should accelerate recruitment into trials substantially,” said Dr. Caselli, professor of neurology at the Mayo Clinic, Scottsdale, Ariz., and associate director and clinical core director of the clinic’s Alzheimer’s Disease Center.
GeneMatch seeks to enroll tens of thousands of people who are aged 55-75 years, and cognitively normal. It’s open to anyone with or without a family history of Alzheimer’s. After completing a brief online educational module, people will be asked to consent to the protocol. Those who agree will receive a cheek swab kit in the mail; samples will be genotyped for APOE status.
Dr. Jason Karlawish
GeneMatch, however, won’t disclose that information to participants. They would learn it only if they enrolled in a study that requires or allows disclosure of that information, said Dr. Jason Karlawish of the University of Pennsylvania, Philadelphia.
“The decision to learn the APOE genotype is a personal one and has to reflect the ethics of informed consent among people who had adequate time to consider their decision,” he said during the teleconference. “We respect the fact that some people want to know this information, and some do not. Our goal for the API APOE4 study is to capture into this study those who want to know.”