What Brain Scans and Gene Studies Can Teach Us About Alzheimer’s

August 24, 2010

Gene researchers have discovered several genes that may play a role in Alzheimer’s, and doctors who study the brain using imaging scans have identified changes in certain brain structures that may also be associated with the disease. Now, scientists have combined both approaches to further refine who may or may not be at increased risk of developing Alzheimer’s. By clarifying the role of genes and brain changes in Alzheimer’s, researchers hope to better understand what causes the disease in the hopes of finding new, more effective treatments or even a cure.

The researchers, from Massachusetts General Hospital in Boston, looked at various genes and brain areas that may be linked to Alzheimer’s in 168 men and women who had Alzheimer’s disease. They also examined the brains and genes of 357 people with mild cognitive impairment, a less serious form of memory loss that can progress to Alzheimer’s, as well as 215 healthy age-matched controls. What they found was that those with certain gene variants were more likely to have changes in areas of the brain linked with memory, including the hippocampus and the amygdala. The findings provide further evidence that genetic factors play a role in Alzheimer’s, and may help doctors better understand what goes wrong in the brains of people with the disease.

“The mechanisms underlying Alzheimer’s disease onset and progression remain largely unexplained,” the authors wrote in the study, which was published in the Archives of Neurology, a medical journal from the American Medical Association. “The demonstration that recently discovered genetic risk factors for Alzheimer’s disease also influence these neuroimaging traits would provide important confirmation of a role for these genetic variants and suggest mechanisms through which they might be acting.”

Scientists have identified genes that play a role in the rare, early-onset form of Alzheimer’s that runs in families and which can strike people as young as their 30s or 40s. But the far more common late-onset form of the disease, which becomes increasingly common in old age, is not as well understood. Studies in twins suggest that genetic factors play a role in late-onset Alzheimer’s, but until recently, only one gene – called APOE, for apolipoprotein E – was shown to influence risk. Having a form of the APOE gene known as APOE-E4 increases your risk, though many who carry the gene still don’t get Alzheimer’s. Several other genes are also suspected of playing a role, though the risks they impart may be smaller than the risk associated with APOE-E4. As yet undiscovered genes may impart different levels of risk.

In addition to genes, changes in the brain have also been linked to Alzheimer’s. A shrinking brain volume, as well as changes in parts of the brain like the hippocampus and amygdala, for example, have been linked to late-onset disease.

In the current study, comparisons of gene variants and change in the brain detected through brain scans revealed that the APOE gene had the strongest association with Alzheimer’s disease. But other genes also showed links with the disease. “Our results indicate that APOE and other previously validated loci for Alzheimer’s disease affect clinical diagnosis of Alzheimer’s disease and neuroimaging measures associated with disease,” the authors wrote. Two gene areas in particular – called BIN1 and CNTN5 – showed possible links with Alzheimer’s onset.

“Elucidation of the genetic risks for late-onset disease beyond the apolipoprotein E locus, discovered in 1993, had been painfully slow until last year,” wrote scientists in an editorial accompanying the study. “These findings, and the genome-wide studies that presaged them, mark a new period of optimism for those of us who study the etiologies of complex diseases of the nervous system. While the drought of genetic findings in Alzheimer’s disease has lasted a long time, the flood of new findings have been a reward worth waiting for.”

By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University

Alessandro Biffi; Christopher D. Anderson; Rahul S. Desikan, et al: Genetic Variation and Neuroimaging Measures in Alzheimer Disease; Archives of Neurology, Vol. 67 (No. 6), June 2010, pages 677-685.
John Hardy; Julie Williams: Identification of Alzheimer Risk Factors Through Whole-Genome Analysis. Archives of Neurology, Vol. 67 (No. 6), June 2010, pages 663-664.


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