A team of researchers from the University of Toronto, Boston University School of Medicine, Duke University and Vanderbilt University, has determined that recent findings suggesting a gene on chromosome 12 was a strong genetic risk factor for Alzheimer's disease cannot be replicated. The results of the investigation will appear in the May issue of Nature Genetics.
It had been reported that the A2M-2 variant of the alpha-2-macroglobulin gene on chromosome 12 was a strong risk factor for Alzheimer's. Investigators had suggested that the increase in risk related to A2M-2 was equal to (or possibly greater than) the strongest known existing risk factor, the e4 variant of apolipoprotein E.
However, the multinational consortium investigating the suspected association could not replicate those results after evaluating A2M in more than 100 Alzheimer's families. Families consisted of multiple members afflicted with the disease. The investigation also included nearly 400 cases of sporadic Alzheimer's disease, and 320 age-matched cognitively normal controls. There was no evidence for an association between the A2M-2 and increased Alzheimer's risk in any patient sample. Researchers determined that the A2M-2 was likely to be a natural genetic variant which does not cause Alzheimer's disease.
"Alzheimer's is a complex disease with multiple genetic risk factors that are difficult to sort out, so it is doubly important that suggested associations can be replicated," said Margaret Pericak-Vance, PhD, professor of medicine and director of the Center for Human Genetics, Duke University Medical Center. "Our results with the e4 variant of apolipoprotein E have been replicated by investigators dozens of times worldwide, but the search continues for the Alzheimer's gene on chromosome 12," she added.
Despite negating the suspected association, the researchers maintain that there
is strong and reproducible evidence for another genetic defect, which does cause
Contact: Steven de Sousa
University of Toronto