Researchers Identify 11 New Genes Tied to Alzheimer's Disease

A massive genetic analysis of Alzheimer's disease has yielded 11 new genes associated with the condition, doubling the number of possible genetics-based therapeutic targets for examination.

Published in the journal Nature Genetics, the results expand researchers' understanding of the disease to incorporate new areas, including the immune system.

"Human genetic studies are being used with increased frequency to validate new drug targets in many diseases," said co-senior author Gerard Schellenberg, director of the Alzheimer's Disease Genetics Consortium and professor of pathology at the University of Pennsylvania. "Here we greatly increased the list of possible drug target candidates for Alzheimer's disease, finding as many new significant genes in this one study as have been found in the last 15 years combined."

The study included a two-stage meta-analysis of more than 74,000 patients and controls from 15 countries. Based on the results, the researchers uncovered genes involved in the immune system and inflammation that corroborated a disease pathway suggested by previous research. Genes related to cell migration, lipid transport and endocytosis were identified as well.

One of the most important discoveries included an association in one of the most complex regions of the genome associated with the immune system and inflammatory response. Known as HLA-DRB5 - DRB1, the area is tied to multiple sclerosis and Parkinon's disease. For this reason, the researchers believe that diseases in which abnormal proteins accumulate in the brain may be caused by a common mechanism, suggesting they may have a common drug target.

"We know that healthy cells are very good at clearing out debris, thanks in part to the immune response system, but in these neurodegenerative diseases where the brain has an inflammatory response to bad proteins and starts forming plaques and tangle clumps, perhaps the immune response can get out of hand and do damage," Schellenberg said.

Despite these strides, the search is one that is far from over, he said. 

"Through this powerful international group as well as our own US collaborations, we'll expand the data set even further to look for rare variants and continue our analysis to find more opportunities to better understand the disease and find viable therapeutic targets," he said. "Large-scale sequencing will certainly play a part in the next phase of our genetics studies."