“The bottom line is you can speculate on a lot of ways that levels of homocysteine affect individuals who have dementia,” Dr. Pericak-Vance added. “If you can measure it early in the disease, it may help to find a way to slow the progression. Of course, it is speculative, but that is where the leap is.”
The investigators noted they have not yet measured homocysteine levels in individuals with the gene variant; however, the plasma samples are available and additional research is planned.
The Future of Genetics
Dr. Pericak-Vance, whose pioneering work led to the discovery of the role of APOE in Alzheimer’s, is hopeful that future genetic mapping studies will provide additional avenues with diagnostic and therapeutic value.
“When this tool [GWAS] first came out, we were naïve. We thought we’d find other very large effects, so we could have small samples sizes of 500 or even less in some of the first GWAS studies,” Dr. Pericak-Vance noted. “We quickly found out that we had probably found most of the larger effects and that we were looking for smaller, although significant, genetic effects in disorders like late-onset Alzheimer’s disease. Our study is what I like to call the next generation of GWAS, where we are embracing larger sample sizes because we are looking for smaller effects.”
“The power of this second-generation GWAS is starting to break through some of the issues we had in trying to identify these somewhat smaller, but much more pervasive types of effects,” Dr. Naj added.
“These studies are just the tip of the iceberg,” Dr. Pericak-Vance concluded, noting the widening scope of GWAS, including the National Institute on Aging’s study on the genetics of Alzheimer’s disease. “We will be looking at hundreds of thousands of samples.… The consolidations with the consortia are making a huge difference, not just in Alzheimer’s disease, but in multiple sclerosis, amyotrophic lateral sclerosis, and stroke, for example. The power of this approach to find what we call ‘susceptibility genes’ and common risk factors is really coming to fruition now.”
—Rebecca K. Abma