11 new gene variants linked to Alzheimer's disease

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In the largest genetic analysis of Alzheimer's ever completed, scientists have discovered 11 new genes that may be tied to the late-onset form of the dementia disease.

Scientists scanned the brains of 74,076 older volunteers with Alzheimer's and others who did not have the disease in 15 countries to come up with their findings. The study was published in Nature Genetics on Oct. 27.

Prior to this study, only 11 gene variants had been linked to late-onset Alzheimer's disease, including one called Apolipoprotein E-e4 (APOE-e4) which appeared to have the strongest impact on risk.

Now, with the latest research, scientists have doubled the known gene variants linked to the disease.

These genes may play a role in how cells function, including how microglial cells (cells that form the support structure of the central nervous system) react to areas of inflammation. Other gene variants were shown to affect brain cell function and synaptic function in the hippocampus, which is the area of the brain responsible for memory and learning.

In particular, researchers say the link to one newly-discovered gene variant known as HLA-DRB5/DRB1 is a landmark finding. It plays a large role in the major histocompatibility complex region of the brain, which is an area of cell surface molecules that control how white blood cells -- which are involved in the immune system -- interact. This area of the brain has also been connected with multiple sclerosis and Parkinson's disease. It could mean that the immune system has something to do with Alzheimer's.

"We've doubled the number of genes discovered and a very strong pattern is emerging," Julie Williams, a professor at the Neuroscience and Mental Health Research Institute at Cardiff University who lead part of the international study, told the BBC. "There is something in the immune response which is causing Alzheimer's disease and we need to look at that."

Scientists also identified 13 other genetic variants that may have potential links to Alzheimer's, but more research needs to be done on these.

The new study was funded by the National Institute of Aging, National Institutes of Health and the International Genomic Alzheimer's Project (IGAP).

"Interestingly, we found that several of these newly identified genes are implicated in a number of pathways," Gerard Schellenberg, professor of pathology and laboratory medicine at the University of Pennsylvania School of Medicine in Philadelphia and a director of one of the major IGAP consortia, said in a press release. "Alzheimer's is a complex disorder, and more study is needed to determine the relative role each of these genetic factors may play."

Alzheimer's disease is a progressive brain disease that affects memory and thinking skills, eventually rendering patients incapable of performing basic activities. It is the most common form of dementia among older people, although about 5 percent of patients will get an early-onset version of the disease before they are 65.

According to the Alzheimer's Association, the disease is the sixth leading cause of death in the U.S., and more than 5 million Americans are currently living with the Alzheimer's.

Not much is known about how the disease starts, but patients with the disease normally have abnormal clumps in their brain known as amyloid plaques and tangled bundles of fibers called neurofibrillary tangles. Some of the gene variants found in the new study have been shown to affect how amyloid protein builds up in the brain, while others played a role in lipid transport and endocytosis, or how proteins are sorted within cells.

Recent studies have also associated poor sleep habits to buildups of brain plaques and people who eat foods high in copper content appear to have higher incidences of Alzheimer's disease.

"This exciting discovery of genes linked with Alzheimer's disease opens up new avenues to explore in the search for treatments for the condition," Dr. James Pickett, head of research for Alzheimer's Society, said in a statement. "This truly global effort has doubled the number of genes linked to Alzheimer's and shows what can be achieved when researchers collaborate. We now need continued global investment into dementia research to understand exactly how these genes affect the disease process."

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